The DOI matches its Crossref record; 48 of the 50 references it cites were found in a registry or an index; 22 of the 41 sources its claims cite were checked for support.
Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses
Open accessAbstract
Incorporating TLR9-inhibitory sequences in the AAV vector genome inhibits immunogenicity and enhances transgene expression in multiple animal models.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
59 Own result · 29 Own interpretation · 21 Own method · 8 No full text of the sources · 7 Partly supported · 4 Supported · 1 Supported so far · 1 Sources not found · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“ocular AAV therapies leading to a permanent reduction in visual acuity following intraocular inflammation (9–11)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
The Results (Inflammatory and Immune Responses; page unavailable) report that mild anterior uveitis in one participant was followed by a persistent 15-letter reduction in visual acuity. This supports a lasting loss after intraocular inflammation, but the paper reports persistence during follow-up, not that the loss was permanent or irreversible. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [10] source
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
The Results report significant retinal inflammation in patient C2 two weeks after AAV treatment, and Online Methods describe it as visually significant vitritis and retinitis. Neither passage establishes a permanent reduction in visual acuity. The Discussion also says the inflammation might have been related to the injection surgery, so its cause is uncertain. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“systemic administration of 1 × 1011 vector genomes (vg) (equivalent to ~4 × 1012 vg/kg, a therapeutically relevant dose in the clinic) of scAAV8.FIX in mice stimulated moderate type I interferon (Ifnb1 and Ifna13) gene expression in the liver at 2 hours post-injection (hpi), the peak time point as previously described (16).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Gene expression comparison section reports hepatic IFN-α/β expression after 1 × 10^11 vg of scAAV2-F.IX in mice, with responses declining after the 2-hour measurement. Figure 1 and the accompanying text identify the tested scAAV8 vector as scAAV8-GFP, not scAAV8.FIX; the time course shown is for scAAV2-F.IX. Thus the source supports the dose, liver response, and 2-hour timing, but not the claim that these interferon results or the peak time were demonstrated specifically for scAAV8.FIX. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA”
- Also stated in: § INTRODUCTION · boosted
“Several studies have demonstrated a central role for Toll-like receptor 9 (TLR9), an immune sensor of DNA, in detecting AAV genomes and triggering innate immune and CD8+ T cell responses (15–18).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
What the sources say
- Supportedcites [15] source
The Discussion (p. 6) identifies viral DNA as the suggested ligand for TLR9 recognition. The results passage spanning pp. 3–4 says viral DNA, rather than contaminating plasmid DNA, is responsible for TLR9 stimulation in plasmacytoid dendritic cells. This supports the claim that the AAV vector genome activates a receptor that senses foreign DNA. (LLM, conf=0.91)
- Supportedcites [16] source
The Discussion states that self-complementary AAV vectors signal through TLR9, which it calls an endosomal receptor for DNA. The section “Role of TLR9 in innate responses to AAV vectors in the liver” says TLR9 recognizes DNA motifs typical of viral or bacterial DNA and that the liver response depends on sensing viral DNA. (LLM, conf=0.93)
- Supportedcites [17] source
The Introduction says TLR9 can recognize unmethylated CpG motifs in DNA packaged within an AAV capsid and describes it as a sensor of bacterial and viral DNA. The Discussion links those motifs in AAV expression cassettes to TLR9-mediated immune responses. No page numbers are provided in our copy. (LLM, conf=0.93)
- Supportedcites [18] source
The Introduction identifies TLR9 as an endosomal DNA receptor involved in innate responses to AAV and links the response to motifs in the vector genome. The “Pattern recognition of AAV vector genome” section says that pDCs sense the viral genome through TLR9. Together, these passages support the paraphrase. (LLM, conf=0.93)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: CpG motifs are present in AAV vector genomes.
- Also stated in: § INTRODUCTION · boosted
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“AAV dose-dependent intraocular inflammation and a few instances of persistent loss of visual acuity have been independently reported in clinical trials following subretinal AAV administration despite prophylactic immunosuppression (9–11).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
What the sources say
- Partly supportedcites [9] sourceExperimental — accuracy not yet measured
The Results (Inflammatory and Immune Responses; page not provided) report inflammation in higher-dose recipients and a persistent 15-letter loss of visual acuity in one participant. The Adverse Events section mentions oral glucocorticoids, but the passages in our copy do not establish that immunosuppression was given prophylactically. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [10] source
- Partly supportedcites [11] sourceExperimental — accuracy not yet measured
The Online Methods report visually significant vitritis and retinitis in patient C2 despite prophylactic prednisolone. The Results identify C2 as a high-dose recipient, but neither the Results nor Discussion establishes a dose-dependent pattern of inflammation. They also do not report persistent visual-acuity loss; the Results instead report an overall improvement in treated eyes at two years. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We confirmed with Tlr9−/− and Myd88−/− mice that the innate immune response to self-complementary AAV was indeed dependent on the TLR9/MyD88 pathway (Fig. 1D and 1E), as previously shown in the literature (15–17).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The research article (p. 3) reports that AAV2-induced type I interferon production by mouse plasmacytoid dendritic cells depended on MyD88, and Figure 5 (p. 4) reports no detectable response in Tlr9−/− or Myd88−/− cells. Our copy does not identify the tested vectors as self-complementary AAV, so it does not establish that qualifier. (LLM, conf=0.88)
- Supportedcites [16] source
In “Innate immune responses to scAAV are TLR9-dependent” (page unavailable), the paper reports that TLR9-deficient mice lacked the measured liver innate-response markers after scAAV administration. “Role of TLR9 in innate responses to AAV vectors in the liver” (page unavailable) describes TLR9 signaling through MyD88, supporting the cited pathway claim. (LLM, conf=0.88)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that Tlr9-deficient mice had a reduced innate cytokine and chemokine response to AAVrh32.33. The Introduction and Discussion (pages unavailable) connect TLR9 to self-complementary AAV and report TLR9/MyD88-dependent recognition of AAV2, but they do not establish that the innate response to self-complementary AAV in mice required both TLR9 and MyD88. (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“in line with a previous intravitreal AAV study in NHPs showing that a 10-fold higher AAV dose only resulted in 2-fold more aflibercept expression (34).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
What the sources say
- Supportedcites [34] source
The Results report that, in NHPs given intravitreal ADVM-022, a 10-fold increase in vector dose produced an approximately 2-fold increase in aflibercept expression in the vitreous humor and retina. The Discussion repeats the same dose-response finding. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We confirmed with Myd88−/− mice that development of CD8+ T cell responses against rh32.33 capsid depended on MyD88(15, 17) (Fig. 2A, middle panel).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
What the sources say
- Partly supportedcites [15] sourceExperimental — accuracy not yet measured
The CD8+ T-cell results (p. 4, Figure 6C–D) show significantly diminished capsid-specific responses in Myd88-deficient mice. But the tested capsid was AAV2, not rh32.33; our copy does not establish the claim for that capsid. (LLM, conf=0.90)
- Partly supportedcites [17] sourceExperimental — accuracy not yet measured
The Results and Figure 2 caption (page unavailable) report reduced capsid-reactive CD8+ T-cell responses in Tlr9-deficient mice. They do not report an experiment in Myd88-deficient mice or establish MyD88 dependence for the rh32.33 capsid response; the Discussion mentions MyD88 only when describing another study’s broader AAV findings. (LLM, conf=0.86)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The immunogenicity challenges of intravitreal administration of AAV are well-recognized compared to subretinal administration (35).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
What the sources say
- Supportedcites [35] source
The Ocular Gene Transfer section explicitly states that subretinal AAV delivery is less immunogenic than intravitreal delivery, based on preclinical models and clinical trials. Its Figure 5 description likewise characterizes subretinal delivery as having low vector immunogenicity and intravitreal delivery as seeming to cause higher immunogenicity and inflammation. (LLM, conf=0.94)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When the order of ODN 2006 and the covalently linked TLR9i sequence was reversed so that the TLR9i sequence was at the 5’ end, a similar reduction in NF-κB response, as well as a reduction in the pro-inflammatory cytokine IL-8, were observed”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ODN TTAGGG, a well-known TLR9i sequence derived from mammalian telomeres (23), did not inhibit the activation of TLR7 or TLR2/6 (sensors of microbial RNA and lipoproteins, respectively) even at high concentration”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“treatment of cells with ODN 2006-TLR9i oligonucleotides (with the ODN 2006 sequence at the 5’ end) resulted in markedly reduced NF-κB response compared to ODN 2006 linked to two separate control sequences not expected to stimulate or inhibit TLR9 (control1 or control2)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The control sequences do not stimulate or inhibit TLR9.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insertion of a 5 nt intervening sequence (AAAAA) between ODN 2006 and selected TLR9i sequences (ODN 2088 or TTAGGG) yielded similar results”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“scAAV8.FIX.io1 treatment also did not elevate interferon gene expression compared to PBS treatment 4 hpi (fig. S2).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the same dose of scAAV8.FIX.io1 elicited no detectable innate immune response in the liver (Fig. 1B).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At a higher dose of 1 × 1011 vg, both rh32.33.GFP and rh32.33.GFP.io2 elicited extremely high capsid-directed T cell responses (~800 – 1000 SFU/million splenocytes) (Fig. 2A, right panel).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While AAV2.aflibercept.io2 did not reduce the incidence of clinical uveitis at 5 × 1011 vg (Fig. 5A; compare Group 4 to 5 and Group 6 to 7)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in our intravenous scAAV8.FIX experiments, we did not detect appreciable CD8+ T cell responses against the AAV8 capsid in an IFN-γ enzyme-linked immune absorbent spot (ELISpot) assay (fig. S4).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The use of prophylactic systemic steroids did not boost aflibercept expression (Fig. 5B, compare Groups 6 and 7 to Groups 4 and 5).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“incorporation of io2 resulted in earlier, more extensive and greater sustained expression of GFP transgene in vivo observable by longitudinal intravital retinal imaging (Fig. 3C and fig. S10A).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Use of prophylactic systemic steroids similarly failed to reduce the incidence of clinical uveitis”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In experimental conditions where an innate immune response was not triggered (administration of 10-fold lower doses of AAV or administration to Myd88−/− mice), scAAV8.FIX.io1 did not lead to an enhancement in FIX expression (Fig. 1H and 1I)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at 6 weeks post-injection (wpi), in all five AAV-injected outbred pigs, AAV8.GFP led to a marked loss, shortening or altered morphology of cone outer segments as labeled by expression of opsins (Fig. 4A and fig. S12A)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subretinal administration of higher-dose AAV in pigs resulted in photoreceptor pathology with microglia and T cell infiltration.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AAV2.GFP.WPRE.io2 elicited lower IL-1β cytokine responses than the unmodified vector in pDCs from nine out of ten donors whose cells responded to AAV infection, and in monocyte-derived dendritic cells (moDCs) from nine out of eleven donors (Fig. 2G, fig. S6).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered AAV2 vector diminishes inflammatory and innate immune responses in primary human plasmacytoid and monocyte-derived dendritic cells
plaindirectn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In these same animals, we detected elevated numbers of CD8+ T cells infiltrating the outer and inner retina in the eye that received AAV8.GFP, but not in the contralateral eye receiving AAV8.GFP.io2 (Fig. 4C and fig. S13C).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“scAAV8.FIX.io1 enhanced human FIX in plasma nearly 3-fold compared to scAAV8.FIX 28 days post-injection (dpi) (Fig. 1G)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“intravitreal injection of higher-dose AAV in macaques, a more immunogenic route of administration, showed that the engineered vector delayed but did not prevent clinical uveitis”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Iba1 signal increased in all AAV-injected eyes (Fig. 4B), suggesting microglia activation and proliferation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“animal 23585 experienced severe vitritis at 2 wpi in its AAV8.GFP-treated eye, but not the contralateral eye treated with AAV8.GFP.io2 (fig. S16 and table S3).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at a dose of 1 × 1010 vg injected into the quadriceps muscle, rh32.33.GFP triggered a range of CD8+ T cell responses against an immunodominant capsid epitope at 21 dpi, with 7 of 10 animals showing positive T cell reactivity (Fig. 2A, left panel).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plaindirectn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Administration of 10-fold lower doses (1 × 1010 vg) of either scAAV8.FIX or scAAV8.FIX.io1 did not trigger interferon responses in the liver”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but we did note a delay by ~22 days for both AAV2.aflibercept and AAV2.aflibercept.io2 (Fig. 5A, compare Group 4 to 6 and Group 5 to 7).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In all injected eyes, there was an area of severe laminar damage surrounding the site of the subretinal injection, which was further surrounded by a region of non-severe laminar disruption (fig. S14).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The combination of io2 and prophylactic systemic steroids gave the latest onset of clinical uveitis at the 5 × 1011 vg dose (Fig. 5A, Group 7)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AAV2.GFP.WPRE.io2 reduced ocular T cell numbers compared to AAV2.GFP.WPRE (Fig. 3B, fig. S8B and fig. S9).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We did not observe enhanced GFP expression in photoreceptors of AAV8.GFP.io2-treated eyes compared to AAV8.GFP (fig. S13C)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We dissociated eye tissues for flow cytometry analysis and surprisingly observed robust CD45+ leukocyte infiltrate, comprising CD3+ T cell and CD8+ T cell populations.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“rh32.33.GFP.io2 muscle sections exhibited higher GFP expression than those with the unmodified vector by immunohistochemical analysis”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These adverse findings were avoided in the contralateral eyes of the same animals that were injected with the engineered vectors.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Iba1 staining of un-injected and vehicle-injected eyes showed a ramified staining pattern outside the outer nuclear layer (ONL), consistent with resting microglia (Fig. 4B).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we did note that AAV2.aflibercept.io2 resulted in an approximately 2-fold enhancement in average aflibercept expression compared to AAV2.aflibercept at both the 1 × 1011 vg and 5 × 1011 vg doses (Fig. 5B, compare Group 2 to 3 and Group 4 to 5).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed the development of comparable amounts of neutralizing antibody (NAb) titers at 28 dpi against AAV8 for both scAAV8.FIX and scAAV8.FIX.io1”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In both animals, laminar changes were similar between right (OD) and left (OS) eyes at 2 wpi (fig. S14B, S14C, S15B and S15C).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparing the 1 × 1011 vg and 5 × 1011 vg groups, there was no evidence of a dose-dependent increase in aflibercept concentrations (Fig. 5B; compare Groups 2 and 3 to Groups 4 and 5)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the vehicle-injected retina, the laminar changes evident at 2 wpi were reduced at 6 wpi (fig. S14A and S15A).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AAV2.GFP.WPRE.io2 also elicited reduced IFN-β cytokine responses compared to AAV2.GFP.WPRE (Fig. 2H).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered AAV2 vector diminishes inflammatory and innate immune responses in primary human plasmacytoid and monocyte-derived dendritic cells
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“expression of the GFP transgene did not appear to impact the overall viability of retinal cells (fig. S10C).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We directly compared AAV vectors with or without TLR9i sequences in experiments encompassing different capsid serotypes, genome configurations, promoters and transgenes, target tissues, routes of administration and animal models, and showed marked reduction of immune responses without changing any other sequences in several models.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No differences in TLR9-inhibitory activity were observed with or without the inclusion of the additional T.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > AAV vectors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“host immune responses pose a major challenge for in vivo gene transfer (1)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [1] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Structural studies recently described two different TLR9i sequences that formed stem-loop structures that fit snugly into the interior of the ring structure of TLR9, preventing dimerization and activation (21).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [21] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, incorporation of a TLR9i sequence within the same molecule as an inflammatory DNA sequence could be more effective at dampening inflammation than administering it as a separate molecule.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“deaths have been reported in a high dose systemic AAV gene therapy trial for children with X-linked myotubular myopathy (14)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [14] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting TLR9i sequences also can function when they are distal to CpG motifs”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting its specificity for TLR9”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This “coupled immunomodulation” strategy may widen the therapeutic window for AAV therapies as well as other DNA-based gene transfer methods.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that other immune factors in addition to TLR9 may contribute to intraocular inflammation in this model.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that io2 might be partially protective against T cell responses at the higher dose”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“implying that clinically observable inflammation incompletely captures the extent of inflammation, particularly tissue-localized immune responses in the retina.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together (see summary in table S3), these data strongly suggest that, unlike the unmodified vector, the engineered vector carrying TLR9-inhibitory sequences could avoid eliciting undesirable innate and adaptive immune cell responses in the retina.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results underscored the value of our approach in evading innate immune responses in human pDCs.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered AAV2 vector diminishes inflammatory and innate immune responses in primary human plasmacytoid and monocyte-derived dendritic cells
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the effects of io2 and steroids were additive.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“linking specific immunomodulatory non-coding sequences to much longer therapeutic nucleic acids can “cloak” the vector from inducing unwanted immune responses in multiple, but not all, models.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that kinetics and impact of immune responses in the subretinal space are different than those in other tissues.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that scAAV8.FIX and scAAV8.FIX.io1 do not have inherently different potencies.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results are consistent with adaptive T cell responses in the eye.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our approach may not translate to complete suppression of all immune responses clinically, depending particularly on dose, route of administration and type of transgene.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results demonstrated that the immune-inhibitory activity of short TLR9i sequences remained functional in a much longer strand of DNA, the AAV vector genome.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma from PBS-injected mice gave signals similar to that of a blank control, demonstrating specificity of the kit for human factor IX.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Mouse liver studies in vivo
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, several ocular AAV gene therapy trials have reported intraocular inflammation at therapeutically relevant doses (see Figure S18 and S19 for analysis).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
What the sources say
- Not matchedcites Figure S18 and S19
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the intravitreal NHP experiment include a single experiment of small and underpowered sample size per group to demonstrate a clinically significant effect, substantial intra-group variability in inflammation and expression, and a lack of understanding of inflammation at the tissue level via histopathology or cell immune phenotype characterization.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the intravitreal NHP experiment include a single experiment of small and underpowered sample size per group to demonstrate a clinically significant effect, substantial intra-group variability in inflammation and expression, and a lack of understanding of inflammation at the tissue level via histopathology or cell immune phenotype characterization.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, they also highlight that other immune factors in addition to TLR9 might contribute to intraocular inflammation in this highly immunogenic route of administration and model.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 41
- The quote only partly states this claim. 1
- Probably not a substantial claim. 20
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“preclinical and clinical studies have demonstrated dose-dependent inflammation, which can reduce efficacy and lead to dose-limiting toxicity (2–8)”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [2] source
- Partly supportedcites [3] sourceExperimental — accuracy not yet measured
The paper’s Abstract reports an acute inflammatory-type toxicity event in one nonhuman primate given high-dose AAV-PHP.B, after lower doses were tolerated, and describes the dose as limiting the vector’s utility. It also mentions immune-mediated liver toxicity reported in human AAV studies. These passages do not establish a general dose-dependent relationship between inflammation and toxicity or show that inflammation reduced efficacy. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [4] source
- Not checked — no full text of the sourcecites [5] source
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites [7] sourceExperimental — accuracy not yet measured
The Results (pages unavailable) report that inflammatory cytokine expression increased with the dose of toxic AAV vectors in mice. The paper’s introductory discussion of clinical trials reports inflammation in five of eight patients given a higher dose and retinal impairment in a separate trial. It does not establish that inflammation was dose-limiting in clinical trials or that it generally reduced treatment efficacy. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [8] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“liver-directed therapies resulting in liver transaminase elevation, which coincides with decreased factor IX (FIX) transgene expression, likely due to AAV capsid-specific cytotoxic T cells destroying transduced hepatocytes (12, 13).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [12] source
- Supportedcites [13] source
The Results (Safety and Efficacy of Peripheral-Vein Infusion of Vector) report that Participant 5’s aminotransferase levels rose while FIX fell from 7% to 3% of normal. The Discussion describes this episode as consistent with AAV8-capsid–specific T-cell–mediated destruction of transduced hepatocytes, matching the claim’s tentative explanation. (LLM, conf=0.91)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Following intravitreal injection of 1 × 1010 vg of AAV2 vectors (fig. S5B), in vivo retinal imaging with non-invasive optical coherence tomography (OCT) clearly detected local inflammation ~10 dpi, featuring subtle optic disc swelling, retinal vascular changes and cellular infiltration of the vitreous cavity (29) (Fig. 3A and fig. S8A).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
What the sources say
- Partly supportedcites [29] sourceExperimental — accuracy not yet measured
The Results sections on Optic Disc Changes and Vascular Changes show that OCT detects optic-disc swelling, vitreous opacities, and inflammatory changes around retinal vessels in mice with experimental autoimmune uveoretinitis. The paper does not establish that intravitreal AAV2 at 1 × 10¹⁰ vg produced these findings at about 10 days; its Methods describe immunisation to induce disease instead. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Plasmacytoid dendritic cells (pDCs) are critical for mounting a TLR9/MyD88-dependent early innate immune response to AAV vectors (15) and they subsequently orchestrate anti-capsid CD8+ T cell responses in vivo by activating conventional DCs to cross-present capsid antigen (18).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered AAV2 vector diminishes inflammatory and innate immune responses in primary human plasmacytoid and monocyte-derived dendritic cells
What the sources say
- Supportedcites [15] source
The citation to this paper is attached to the first clause, about pDCs and the early innate response; the cross-presentation clause cites a different source. The Introduction (p. 2) says AAV activates pDCs to produce type I interferons through TLR9 and MyD88, and the Results (p. 3) show that pDCs lacking either component failed to produce those interferons after AAV stimulation. (LLM, conf=0.92)
- Supportedcites [18] source
Citation (18) is attached to the second clause, about pDCs orchestrating anti-capsid CD8+ T-cell responses; the early innate-response clause cites a different source. In the discussion section, the paper says pDC sensing of the viral genome provides the signal that induces presentation by cDCs. The results section likewise identifies pDC TLR9 activity as the required activation signal and cDCs as primarily responsible for antigen presentation. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ODN 2006-TTAGGG blocked ~80% of induced NF-κB response, while co-administration of ODN 2006 and TTAGGG only inhibited ~35% of induced NF-κB response”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > TLR9i sequences efficiently inhibit inflammation when applied in cis with CpG-containing oligonucleotides
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we tested a similar dose of a single-stranded vector expressing human FIX under the control of a ubiquitous CAG promoter (rh32.33.FIX or rh32.33.FIX.io2) intramuscularly, and likewise observed that the engineered vector augmented human FIX in vivo (Fig. 2F).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, while both AAV8.GFP-treated eyes in animals 23585 and 23586 showed substantial microglia and T cell infiltration in the retina via histology, only the former presented with vitritis during clinical examinations”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 6 wpi, both AAV8.GFP.io2-injected right eyes (OD) had reduced areas of severe laminar damage, similar to the vehicle treated eye. In contrast, the large areas of severe laminar damage were maintained in both AAV8.GFP-treated left eyes (OS).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, uveitis occurred in a dose-dependent manner (Fig. 5A; compare Group 2 to 4 and Group 3 to 5), beginning 2 – 6 weeks after AAV dosing for the majority of animals that experienced inflammation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas scAAV8.FIX stimulated macrophage infiltration of the liver, scAAV.FIX.io1 avoided immune cell infiltration (Fig. 1F).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Flow cytometry analysis of dissociated retinas confirmed a multi-fold boost in the number of GFP+ retinal cells, and further revealed that GFP mean fluorescence intensity was higher on a per cell basis (Fig. 3D and fig. S10B).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, we observed in two of five animals - animals 23585 and 23586 – apparent loss or retraction of cone pedicles (the synaptic terminals of cone photoreceptors important for transferring the light signal onto the dendrites of bipolar cells and horizontal cells) with AAV8.GFP; no such loss was observed in eyes injected with AAV8.GFP.io2 (see Fig. 4A and fig. S12B).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed robust CD8+ T cell infiltration into muscle samples from rh32.33.GFP-injected animals, and approximately one-third were positive for granzyme B − a marker for activated cytotoxic T cells − while no CD8+ T cell infiltration was observed in any of the eight rh32.33.GFP.io2-injected muscle samples”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“incorporation of io2 at this dose delayed clinical uveitis by ~10 days both with and without prophylactic systemic steroids, although these differences did not reach statistical significance.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Strikingly, the unmodified vector AAV8.GFP stimulated robust microglia infiltration into the ONL (extension of microglial processes into the photoreceptor layer, as well as infiltration of amoeboid-shaped cells, indicative of activated microglia) in animals 23585 and 23586, which was not observed for the engineered vector AAV8.GFP.io2 in the contralateral eyes (Fig. 4B and fig. S13B).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells from only a few donors responded to AAV infection with IL-6 cytokine responses and we did not observe statistically significant differences between the two vectors (fig. S7).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered AAV2 vector diminishes inflammatory and innate immune responses in primary human plasmacytoid and monocyte-derived dendritic cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“contralateral eyes injected with AAV8.GFP.io2 showed substantially better preservation of cone outer segments and appeared more morphologically similar to un-injected or vehicle-injected eyes, which was verified by quantification of the length of GFP+ cones (fig. S13A).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues, including liver, muscle and retina.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed substantial variation in aflibercept concentrations among animals of each group and did not detect any statistically significant differences between groups.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, we observed no impact on the formation of Nabs against AAV capsid and reduced effects on preventing anti-capsid T cell responses in highly immunogenic settings.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, incorporation of TLR9i sequences suppressed the extent of ocular T cell infiltrate induced by intravitreal AAV in mice, but the response was not eliminated.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No substantial differences in viral yield (viral titer × volume) were observed between unmodified vectors and corresponding engineered vectors for >20 purifications, suggesting that insertion of the described sequences did not hamper viral packaging.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > AAV vectors
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the binding site of TLR9i oligonucleotides on TLR9 partially overlapped with that of CpG DNA, and the TLR9i oligonucleotide tested possessed higher binding affinity for TLR9 than CpG DNA”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [21] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition to TLR9, TLR2 is implicated in sensing the AAV capsid (20).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [20] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This inflammatory response is consistent with the anatomical distribution and phenotype seen in ocular clinical trials but has not been reported before in mice (5).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
What the sources say
- Not checked — no full text of the sourcecites [5] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, our results indicated that intravitreal AAV administration stimulated ocular T cell infiltration in mice, and that incorporation of io2 diminished local T cell numbers while allowing greater transgene expression by boosting both the number of GFP+ cells and the degree of GFP expression per transduced cell.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations on the magnitude and kinetics of transgene expression imply that evasion of TLR9-mediated immune responses enhanced viral transduction and/or survival of transduced retinal cells.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data demonstrated that subretinal administration of higher doses of AAV triggered photoreceptor pathology and the engineered vector reduced the induction of such pathology.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Iba1 signal increased in all AAV-injected eyes (Fig. 4B), suggesting microglia activation and proliferation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ocular inflammation also may reduce efficacy directly by inducing pathology in retinal cells, or indirectly by mandating the use of lower, sub-optimal doses.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector reduces ocular T cell infiltration while augmenting number of transgene-expressing retinal cells and expression of transgene per cell in mice
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“large animal studies recapitulate intraocular inflammation observed in clinical trials (30, 31), and pig and human eyes share similarities in size and morphology (32).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Subretinal injection of AAV8 in a pig model elicits cone photoreceptor pathology with microglia and T cell infiltration in the retina, which are evaded by engineered vector
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results indicated that incorporation of io1 into an scAAV vector evaded innate immune responses in the liver and enhanced transgene expression following intravenous administration.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io1 into a self-complementary AAV8 vector reduces interferon responses and macrophage infiltration in mouse liver and boosts factor IX expression
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results indicated that incorporation of io2 into a single-stranded AAV vector reduced CD8+ T cell responses and infiltration and enhanced transgene expression following intramuscular AAV administration.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the presence of io2 prevented capsid-directed CD8+ T cell responses and infiltration”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Incorporation of io2 into an AAVrh32.33 vector reduces anti-capsid T cell responses and cytotoxic T cell infiltration in mouse muscle and enhances gene transfer
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“As single-stranded AAV vectors have an equal chance of packaging positive or negative strands of the viral genome, we added both sense and anti-sense TLR9-inhibitory sequences. This strategy ensured that all packaged AAV genomes will carry copies of TLR9-inhibitory sequences in the right orientation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > AAV vectors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may reflect incomplete TLR9 blockade with io2, or a potential influence of other non-TLR9 factors that are operative within and specific to the ocular environment.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest that the engineered vector might enhance transgene expression and delay clinical uveitis in NHP eyes.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > RESULTS > Engineered vector delays, but does not prevent, intraocular inflammation following intravitreal AAV2 administration in non-human primates
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the intravitreal mouse study, laterality of injected eyes was randomized, and investigators were masked to the vector type throughout intervention and analysis.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Some data points were excluded from analyses due to: a sample with abnormal amplification curve during qPCR, an IFN-γ ELISpot well with too many spots to count for the plate reader, and lack of immune responses for some PBMC donors.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We postulate that incorporation of TLR9i sequences reduces the immune response by out-competing CpG motifs in the same vector genome for TLR9 binding, and consequently prevents TLR9 dimerization and activation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: AAV is taken up by TLR9-positive immune cells such as plasmacytoid dendritic cells, and its genome can be exposed in endosomes and sensed by TLR9.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All in vitro experiments were performed at least twice independently.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Animals were assigned randomly by weight to each group to achieve similar group mean body weights.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Intravitreal injection of AAV in NHPs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Laterality of injected eyes was randomized, and investigators were masked to the vector type throughout intervention and analysis.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Mouse intravitreal AAV injection and clinical assessment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, the approach may not block anti-transgene immune responses, as TLR9 is not thought to be essential for such responses.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: TLR9 is not essential for anti-transgene immune responses.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, vector preps had < 1EU/ml of endotoxin using a limulus amebocyte lysate assay (ToxinSensor Chromogenic LAL Endotoxin Assay Kit, Genscript).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > AAV vectors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Laterality of injected eyes was randomized, and investigators were masked to the vector type throughout intervention and analysis.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Mouse intravitreal AAV injection and clinical assessment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the intravitreal NHP study, the veterinary ophthalmologist was masked to the test article when performing injections and scoring of inflammation.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the intravitreal NHP experiment utilized a secreted human transgene protein, and we did not attempt to measure if anti-drug antibodies (ADAs) formed in the NHPs.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No pre-specified effect size was assumed and in general three to six replicates, animals, or donors for each condition was used per experiment.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All other studies and experiments were not performed blinded.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“ELISpot plates were evaluated in blinded fashion (ZellNet Consulting, Inc.) using an automated ELISpot reader system (KS ELISpot reader, Zeiss) with KS ELISpot software version 4.9.16.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > IFN-γ T cell ELISpot assays
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For the subretinal pig study, the retinal surgeon performing the injections was blinded to the test article, and similarly, clinical examinations and scoring of inflammation were performed blinded.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The retinal surgeon performing the injections was blinded to the test article, and similarly, clinical examinations and scoring of inflammation were performed blinded.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Subretinal injection of AAV in domestic pigs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The retinal surgeon performing the injections was blinded to the test article, and similarly, clinical examinations and scoring of inflammation were performed blinded.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Subretinal injection of AAV in domestic pigs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Limitations of the intravitreal NHP experiment include a single experiment of small and underpowered sample size per group to demonstrate a clinically significant effect, substantial intra-group variability in inflammation and expression, and a lack of understanding of inflammation at the tissue level via histopathology or cell immune phenotype characterization.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The plate evaluation process including the setup of optimal reading parameters followed the International guidelines on ELISpot plate evaluation (42).”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > IFN-γ T cell ELISpot assays
What the sources say
- Not checked — no full text of the sourcecites [42] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sample size was chosen empirically based on results of previous studies.”
§ Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses > MATERIALS AND METHODS > Study design
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
CpG motifs are present in AAV vector genomes.
“which also are present in AAV vector genomes”
The paper relies on this without support.
Intravitreal administration is more immunogenic than subretinal administration in the eye.
“a more immunogenic route of administration in the eye compared to subretinal administration”
The paper relies on this without support.
Subretinal AAV in the mouse eye is minimally immunogenic.
“In the mouse eye, subretinal AAV has been regarded as minimally immunogenic”
The paper relies on this without support.
The control sequences do not stimulate or inhibit TLR9.
“two separate control sequences not expected to stimulate or inhibit TLR9”
The paper relies on this without support.
AAV is taken up by TLR9-positive immune cells such as plasmacytoid dendritic cells, and its genome can be exposed in endosomes and sensed by TLR9.
“During in vivo gene therapy, AAV can be taken up by TLR9+ immune cells such as plasmacytoid dendritic cells and the vector genome may become exposed during endosomal trafficking and detected by TLR9.”
The authors state this as an assumption.
A period of 4 weeks to 3 months gives stable or near-stable transgene expression.
“Our experimental models tested the effects of io1 and io2 for 4 weeks to 3 months, a time period assumed to give stable or near-stable expression.”
The paper relies on this without support.
TLR9 is not essential for anti-transgene immune responses.
“as TLR9 is not thought to be essential for such responses.”
The paper relies on this without support.
The human factor IX ELISA kit had a sensitivity of at least 0.78 ng/ml.
“The kit had a sensitivity of at least 0.78 ng/ml.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Preclinical investigations utilizing mice have limited utility in predicting severe adverse events, as outcomes from AAV2 IVT injections without immunomodulation predominantly reveal mild to moderate inflammation accompanied by ocular infiltration of CD45+ peripheral immune cells, including T cells (30, 32–34).”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Preclinical investigations utilizing mice have limited utility in predicting severe adverse events”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Additionally, persistent inflammation has been observed in patients receiving high doses of both AAV2 or AAV2.7m8, despite steroid treatment (27, 30).”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Limitations associated with IVT delivery of AAV vectors are well documented, including dose-dependent IOI, suboptimal effect of oral and topical corticosteroid treatments (27, 30), and inefficient transduction of outer retinal layers, in which vector genomes are present but transgene expression is low.”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“On the other hand, studies in non-human primates (NHPs) have shown that IVT AAV2 administration at the dose of 5×1011 vg/eye can induce uveitis in the presence of prophylactic systemic methylprednisolone (30).”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“However, this observation was consistent with previous reports showing that reducing retinal inflammation may benefit transgene expression (30, 51).”
From Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses (2026) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“To evaluate immune responses toward vector treatment, we stained-cryosectioned retinas with anti-IBA1 (Fig. 4), which stains microglia, the resident immune cells of the retina that is used as a marker for immune responses in AAV-treated eyes [9,13,45].”
From The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2 (2024) · cites this paper as [45]
The cited source says what the claim attributes to it.
In the citing paper
“in their study they engineered a vector that can evade activation of Toll-like Receptor 9 (TLR9), thereby reducing activation of both the innate and T-cell response and inflammation [35].”
From Characterization of anti-AAV2 neutralizing antibody levels in sheep prior to and following intravitreal AAV2.7m8 injection (2024) · cites this paper as [35]
In the citing paper
“Characterization of the early ocular immune responses to AAV in young animals demonstrates activation of resident microglia,10,11,12 antigen presentation,10 and lymphocyte infiltration.3,4,5,10,12”
From Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age (2025) · cites this paper as [5]
In the citing paper
“Nevertheless, it is evident within pre-clinical and clinical studies that AAV-induced inflammation is a limiting obstacle impacting safety and durable efficacy.3,4,5,6”
From Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age (2025) · cites this paper as [5]
In the citing paper
“To date, studies to understand and develop approaches to control inflammation (e.g., modifying vector—capsid and sequence) have not sought to delineate sex differences.5”
From Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age (2025) · cites this paper as [5]
In the citing paper
“Previous work has shown that AAV-mediated inflammation in the eye predominantly comprises CD3+ T cells, indicating an adaptive immune response,3,5 a response mediated by posterior lymphatic drainage after IVT injection.26”
From Characterization of the ocular inflammatory response to AAV reveals divergence by sex and age (2025) · cites this paper as [5]
In the citing paper
“In another study, it has been reported that the incorporation of TLR9-inhibitory (TLR9i) DNA sequences in the AAV genome can reduce immune responses in mice and pigs [155].”
From Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer (2023) · cites this paper as [155]
In the citing paper
“More recent work has highlighted the role of innate immune system in response to AAV therapeutics (42–46)”
From Pre-existing humoral immunity and complement pathway contribute to immunogenicity of adeno-associated virus (AAV) vector in human blood (2022) · cites this paper as [45]
In the citing paper
“An alternative approach to eliminate TLR9 signaling is to include TLR9 inhibitory DNA sequences in the vector construct, as recently been shown by Chan et al. (54).”
From Effect of CpG Depletion of Vector Genome on CD8+ T Cell Responses in AAV Gene Therapy (2021) · cites this paper as [54]
In the citing paper
“Incorporating TLR9 inhibitory sequence (TTAGGG motif) in AAV vectors reduced CTL responses and enhanced transgene expression in mice and pigs (158).”
From A versatile toolkit for overcoming AAV immunity (2022) · cites this paper as [158]
In the citing paper
“However, this strategy only delayed but could not prevent CTL response in NHPs, indicating that immune factors other than TLR9 contributed to intra-ocular in fl ammation in NHPs.”
From A versatile toolkit for overcoming AAV immunity (2022) · cites this paper as [158]
In the citing paper
“In the context of AAV gene therapy, various studies have reported the upregulation and secretion of both IL-1a and IL-1b cytokines in different disease models.”
From Innate immune sensing of adeno-associated virus vectors (2024) · cites this paper as [33]
In the citing paper
“Furthermore, by incorporating a TLR9 inhibitory sequence in AAV expression cassette, Chan et al. have shown a reduced immune response in murine and swine models, representing an alternative strategy to the CpG depletion approach.”
From Innate immune sensing of adeno-associated virus vectors (2024) · cites this paper as [33]
In the citing paper
“Chan et al. concluded that there might be additional pathways mediating these immune responses.”
From Innate immune sensing of adeno-associated virus vectors (2024) · cites this paper as [33]
In the citing paper
“However, immune responses were still observed at high vector doses, for instance, in macaques injected through intravitreal route.TLR9 inhibition merely delayed immune-mediated clinical uveitis in these experimental animals.”
From Innate immune sensing of adeno-associated virus vectors (2024) · cites this paper as [33]
In the citing paper
“Immune responses are also commonly observed using viral vectors and with mRNA transfections (42–44).”
From Subretinal therapy: technological solutions to surgical and immunological challenges (2022) · cites this paper as [44]
In the citing paper
“To evade the immune system, George Church and colleagues recently reported the generation of engineered AAV vectors that are intrinsically less immunogenic.”
From The Ocular Gene Delivery Landscape (2021) · cites this paper as [77]
In the citing paper
“They achieved this by incorporating immunomodulatory noncoding sequences to “cloak” the vector from immune responses [77].”
From The Ocular Gene Delivery Landscape (2021) · cites this paper as [77]
In the citing paper
“The high prevalence and cross-reactivity of neutralising AAV antibodies [239] indicates that methods to mitigate anti-AAV immunity will be necessary before the safety and efficacy of high-dose intravitreal viral vector-based gene therapy can be fully evaluated [267].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [267]
In the citing paper
“Although limitations of this approach were noticed,29 alternative pathways that may lead to CD8+ T cell activation have been unknown.”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [29]
In the citing paper
“To circumvent recognition of the AAV genome by TLR9, development of CpG-depleted expression cassettes has become a major focus for clinical applications, while incorporation of TLR9 inhibitory sequences has been proposed as an alternative strategy.28,29,30”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [29]
In the citing paper
“One approach relies on the incorporation of short DNA oligonucleotides into the vector genome, which antagonizes TLR9 as described by Chan et al. 2021.”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“Inhibitory oligonucleotides with stem-loop secondary structures have recently been used to antagonize TLR9 activation [13].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“These engineered vectors appeared to be inherently less immunogenic and elicited strongly decreasing innate and T cell responses to the vector along with enhanced transgene expression [13].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“These engineered vectors appeared to be inherently less immunogenic and elicited strongly decreasing innate and T cell responses to the vector along with enhanced transgene expression [13].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“These engineered vectors appeared to be inherently less immunogenic and elicited strongly decreasing innate and T cell responses to the vector along with enhanced transgene expression [13].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“Using this deimmunized vector, they were able to show that intraocular inflammation following rAAV subretinal injection of 4 × 10 11 vg per eye was mitigated.”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [13]
In the citing paper
“In the context of gene therapy, inflammatory reactions against adeno-associated viral (AAV) vectors used to deliver gene therapy components have been described.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [14]
In the citing paper
“These reactions may be mediated, in part, by innate immune responses against the vector genome which attract CD8+ T-cells and drive inflammation14.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [14]
In the citing paper
“Because ODN 2088 and many other TLR9 inhibitors are short oligonucleotides, they can be introduced into host cells as part of the viral genome, in cis, an approach that has recently been used to reduce or delay AAV-induced toxicity in the retina in pigs and macaques, respectively.61”
From An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission (2024) · cites this paper as [61]
Citations
Cites
(2005) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2005.03.057 · Cited by 4,396
Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy
Mendell, J. R., Al-Zaidy, S., Shell, R., Arnold, W. D., Rodino-Klapac, L. R., Prior, T. W., Lowes, L., Alfano, L., Berry, K., Church, K., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1706198 · Cited by 2,381
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163 · cited 1×
“Examples include ocular AAV therapies leading to a permanent reduction in visual acuity after intraocular inflammation (9–11) and liver-directed therapies resulting in liver transaminase elevation, which coincides with decreased factor IX (FIX) transgene expression, likely due to AAV capsid–specific cytotoxic T cells…”
BackgroundSelf-citationRussell, S., Bennett, J., Wellman, J. A., Chung, D. C., Yu, Z.-F., Tillman, A., Wittes, J., Pappas, J., Elci, O., McCague, S., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31868-8 · Cited by 1,952 · cited 1×
“Recent successes in AAV gene therapy in the clinic (4, 36) highlight the potential for in vivo gene therapy to treat multiple types of disorders.”
BackgroundAdenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1108046 · Cited by 1,864
Self-citationGene therapy - promises, problems and prospects
Verma, I. M., & Somia, N. (1997) · Nature · doi:10.1038/38410 · Cited by 1,681 · cited 2×
“Gene therapy holds exciting promise for treating many genetic disorders, but host immune responses pose a major challenge for in vivo gene transfer (1).”
BackgroundMethodMicroglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Olson, J. K., & Miller, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3916 · Cited by 1,215 · cited 1×
“Microglia are the resident innate immune cells of the retina and reports in the literature suggest that CNS microglia can respond to CpG ligands (33).”
BackgroundBeutler, B. A. (2009) · Blood · doi:10.1182/blood-2008-07-019307 · Cited by 840 · cited 1×
“TLRs are a family of innate immune sensors conserved across mammalian species that are found on endosomal or plasma membranes of immune cells (19).”
BackgroundHinderer, C., Katz, N., Buza, E. L., Dyer, C., Goode, T., Bell, P., Richman, L. K., & Wilson, J. M. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.015 · Cited by 814
Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses
Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J., & Wilson, J. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/595830 · Cited by 808 · cited 1×
“In vitro AAV neutralizing antibody (NAb) assays were performed on plasma samples 28 d after PBS or 1 x 10(11) vg AAV8 administration as previously described (41) with the following modifications: plasma samples were heat-inactivated and diluted 1:40 in DMEM followed by five 3-fold serial dilutions.”
MethodSelf-citation
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
Self-citationAdeno-associated virus as a delivery vector for gene therapy of human diseases
Wang, J.-H., Gessler, D. J., Zhan, W., Gallagher, T. L., & Gao, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01780-w · Cited by 904
“436 Pharmacological inhibitors of innate signaling pathways are another option.”
BackgroundSelf-citationAAV vectors: The Rubik’s cube of human gene therapy
Pupo, A., Fernández, A., Low, S. H., François, A., Suárez-Amarán, L., & Samulski, R. J. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.09.015 · Cited by 382
“204 205 – 207 Faust et al. showed that CpG-depleted AAVrh32.”
BackgroundMultiyear Factor VIII Expression after AAV Gene Transfer for Hemophilia A
George, L. A., Monahan, P. E., Eyster, M. E., Sullivan, S. K., Ragni, M. V., Croteau, S. E., Rasko, J. E. J., Recht, M., Samelson‐Jones, B. J., MacDougall, A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2104205 · Cited by 248
Self-citationAdeno-Associated Virus Technologies and Methods for Targeted Neuronal Manipulation
Haery, L., Deverman, B. E., Matho, K. S., Cetin, A. H., Woodard, K., Cepko, C. L., Guerin, K. I., Rego, M. A., Ersing, I., Bächle, S. M., et al. (2019) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2019.00093 · Cited by 220
Self-citation
Metadata
- Authors
- Chan, Y. K., Wang, S. K., Chu, C. J., Copland, D. A., Letizia, A. J., Costa Verdera, H., Chiang, J. J., Sethi, M., Wang, M. K., Neidermyer, W. J., Chan, Y., Lim, E. T., Graveline, A. R., Sanchez, M., Boyd, R. F., Vihtelic, T. S., Inciong, R. G. C. O., Slain, J. M., Alphonse, P. J., Xue, Y., Robinson-McCarthy, L. R., Tam, J. M., Jabbar, M. H., Sahu, B., Adeniran, J. F., Muhuri, M., Tai, P. W. L., Xie, J., Krause, T. B., Vernet, A., Pezone, M., Xiao, R., Liu, T., Wang, W., Kaplan, H. J., Gao, G., Dick, A. D., Mingozzi, F., McCall, M. A., Cepko, C. L., & Church, G. M.
- Affiliations
- Harvard University (US)
- University of Bristol (GB)
- Inserm U974, Sorbonne Universite, Paris 75651, France.
- Ally Therapeutics (United States) (US)
- Charles River Laboratories (United States) (US)
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
- University of Louisville (US)
- University of Massachusetts Chan Medical School (US)
- Massachusetts Eye and Ear Infirmary (US)
- National Institute for Health and Care Research (GB)
- Inserm (FR)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chan, Ying Kai
- Church, George M.
- ORCID
- Chan, Ying Kai
- Wang, Sean K.
- Chu, Colin J.
- Copland, David A.
- Letizia, Alexander J.
- Costa Verdera, Helena
- Chiang, Jessica J.
- Sethi, Meher
- Chan, Yingleong
- Lim, Elaine T.
- Graveline, Amanda R.
- Sanchez, Melinda
- Inciong, Rolando Gian Carlo O.
- Slain, Jared M.
- Alphonse, Priscilla J.
- Xue, Yunlu
- Robinson-McCarthy, Lindsey R.
- Tam, Jenny M.
- Adeniran, Janelle F.
- Muhuri, Manish
- Tai, Phillip W. L.
- Vernet, Andyna
- Xiao, Ru
- Liu, Tina
- Wang, Wei
- Kaplan, Henry J.
- Gao, Guangping
- Dick, Andrew D.
- Mingozzi, Federico
- McCall, Maureen A.
- Cepko, Constance L.
- Church, George M.
- Venue
- Science Translational Medicine
- Published
- 2021-02-10
- Volume
- 13
- Issue
- 580
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC8409505
- OpenAlex
- W3126525679
- Cited by
- 215
- References
- 50
- Citations by year
- 2026: 37 · 2025: 37 · 2024: 39 · 2023: 37 · 2022: 41 · 2021: 22
- FWCI
- 19.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Explore Bristol Research (acceptedVersion, other-oa)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health (RM1 HG008525, EY026158)
- Howard Hughes Medical Institute
- National Eye Research Centre (BRI 021)
- European Research Council (ERC-CoG-617432)
- Wyss Institute for Biologically Inspired Engineering of Harvard University
- Underwood Trust (8064)
- Kentucky Lions Eye Research Endowed Chair
- Ally Therapeutics
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- adeno-associated virus vectors, innate immune evasion, T cell response, uveitis, subretinal injection, intravitreal injection, non-coding sequences
- MeSH terms
- Dependovirus, Animals, Genetic Vectors, Immunity, Innate, Swine, Genetic Therapy, Gene Transfer Techniques, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-29, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-29 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
