The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 18 of the 59 sources its claims cite were checked for support.
Nonviral delivery of self-amplifying RNA vaccines
Open accessAbstract
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Nonviral delivery of a 9-kb self-amplifying RNA encapsulated in lipid nanoparticles (LNP/RNA) increased reporter gene expression and immunogenicity compared with unformulated RNA. In mice and cotton rats, LNP/RNA elicited potent RSV-F-specific humoral and cellular responses and protection from RSV challenge comparable to viral replicon particle delivery.
Key findings
- LNP encapsulation protected self-amplifying RNA from RNase degradation and improved in vivo expression: 0.1 μg LNP/RNA increased serum SEAP over 1 μg naked RNA and reduced animal-to-animal variability.
- After two intramuscular immunizations, 0.1 μg LNP/RNA encoding RSV-F elicited F-specific IgG GMT 26,170 versus 2,292 for 1 μg naked RNA; 1 μg LNP/RNA was equivalent to 1 × 10⁶ IU VRPs (GMT 10,478), and seroconversion occurred after a single LNP/RNA dose as low as 0.01 μg RNA.
- In cotton rats, LNP/RNA boosted F-specific IgG approximately 8-fold (GMT 4,355 vs. 526) and RSV neutralization titers 10-fold (GMT 1,493 vs. 154) relative to the same dose of naked RNA, equivalent to 5 × 10⁶ IU VRPs (GMTs 5,861 and 1,690); all self-amplifying RNA vaccines reduced lung viral load >1,000-fold versus controls after intranasal RSV challenge.
- LNP/RNA elicited slightly elevated F-specific IgG2a relative to IgG1 and potent antigen-specific IFN-γ-producing CD4⁺ and CD8⁺ T cell responses; functional immune responses against HIV antigens were also observed (Fig. S5).
Methods
- Preclinical vaccine study using a self-amplifying RNA based on an alphavirus genome, produced by T7 RNA polymerase transcription from linear pDNA and encapsulated in lipid nanoparticles via an ethanol dilution process using DLinDMA, DSPC, cholesterol, and PEG-DMG 2000.
- Female BALB/c mice (8–10 wk, ~20 g) and female cotton rats were immunized intramuscularly on days 0 and 21; cotton rats were challenged intranasally with 1 × 10⁵ pfu RSV 4 wk after the final immunization.
- Main analyses included serum SEAP and luciferase bioluminescence, RSV-F-specific IgG/IgG1/IgG2a ELISA, RSV neutralization titers, T cell cytokine flow cytometry, and lung viral load; statistics used one-way ANOVA or Kruskal-Wallis with Dunn’s posttest at 95% confidence.
Limitations
- Stated: immunogenicity at submilligram doses in larger species “remains to be directly tested”; the mechanism of action is not fully elucidated, and studies are underway to identify transfected cells and explain why LNP delivery gives longer expression than VRP delivery.
- Stated: production of larger (~9 kb) self-amplifying RNA adds challenges, though the authors call them “not insurmountable.”
- Evident from the text: all efficacy and challenge data are from mice and cotton rats, with no human or nonhuman primate data reported for this LNP/RNA vaccine.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
31 Own result · 16 No full text of the sources · 14 Own interpretation · 7 Supported · 6 Partly supported · 5 No basis given · 2 Supported so far · 1 Own method · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, naked RNA vaccines suffer from limited potency, in part due to RNA instability in vivo, related to the presence of degradative enzymes in tissues (15).”
What the sources say
- Supportedcites [15] source
The Background states that ubiquitous ribonucleases rapidly degrade mRNA and that this instability limits the efficacy of mRNA-based therapies. The Conclusion applies that concern to mRNA vaccination, proposing protection from RNases to improve vaccine efficacy. (LLM, conf=0.92)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, for infant RSV vaccine development, safety considerations favor replicating (or selfamplifying) vaccine candidates over subunit approaches (33).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Supportedcites [33] source
The “Subunit proteins” section says subunit vaccines face significant regulatory hurdles in seronegative infants and raises theoretical concerns about vaccine-enhanced disease relative to live-attenuated viruses or gene-based vectors. This supports the claim as a statement about safety considerations, not as proof that every replicating candidate is safe. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Similarly, EP-mediated delivery of pDNA has been shown to be broadly effective (26) and thus was used as the benchmark for pDNA delivery.”
What the sources say
- Supportedcites [26] source
The “Electroporation Enhanced DNA Vaccine Delivery” section reports a 100–1000-fold enhancement in plasmid delivery and gene expression compared with DNA delivery without EP. The “Translating In vivo Expression to Immunogenicity and Efficacy” section describes enhanced responses across numerous vaccine candidates and animal disease models. Together, these support the broad effectiveness attributed to EP-mediated pDNA delivery; page numbers were not supplied. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“VRPs have been shown to be potent in nonhuman primates and humans at a 100-fold higher dose (1 × 10 8 IU) (22,25), and thus we anticipate that this unique RNA vaccine will be immunogenic at submilligram doses in larger species, but this remains to be directly tested.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
Materials and Methods reports a VRP dose of 1 × 10^8 IU in rhesus macaques, and the Results and Discussion report immune responses and protection with a VRP-prime/Env-protein-boost regimen. The copy does not establish potency in humans or that this dose was 100-fold higher than a comparison dose; it also reports that VRP alone did not protect the macaques. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [25] 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The current costs of clinical manufacturing of pDNA are on the order of $50-100 per milligram (1-10 g scale) (26).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Supportedcites [26] source
The “Prospects for Clinical Efficacy and Product Development Success” section states that current small-scale cGMP DNA manufacturing costs are approximately $50–100 per milligram at a 1–10 g manufacturing scale. This matches the cited claim about clinical pDNA manufacturing costs. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — 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
“Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA.”
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
“This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors.”
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
“This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral 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.
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 contrast, the naked control RNA was degraded by RNase A (Fig. 1C, lane 3 compared with lane 2).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Importantly, the immunogenicity and protective efficacy generated by 1 μg LNP/RNA was equivalent to the responses elicited by the VRP delivery technology.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plain- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 38
- Probably not a substantial claim. 9
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although plasmid DNA (pDNA) vaccines have proven to be a flexible platform and are broadly effective in small animal models, they have generally lacked potency in human clinical trials (2).”
What the sources say
- Supportedcites [2] source
The Preclinical studies section reports protective immunity against a broad range of pathogens in small-animal studies and describes applications beyond infectious disease. The DNA vaccine platform: room for improvement section says responses in humans have been significantly weaker than in mice, and Initial DNA vaccine studies in humans says greater potency is needed. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, with increasing life expectancy in high-income countries and newly emerging infections and poverty in low-income countries, new technologies will be required to address changing vaccine needs (1).”
What the sources say
- Supportedcites [1] source
The Main section identifies an aging society, emerging infections, and poverty in low-income countries as changing health needs. It also says emerging infections require appropriate technologies and that research into novel vaccine technologies remains a priority. No page numbers are available in our copy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“VRPs are potent vaccines in mice (10,11), nonhuman primates (11,22), and humans (25).”
What the sources say
- Supportedcites [10] source
The Discussion reports potent vaccine responses in mice, and the Abstract states that VEE replicon particles induced potent, protective immune responses in primates. In the citing sentence, this source is cited for mice and nonhuman primates; the human claim is assigned to citation 25, not this paper. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [11] source
- Partly supportedcites [22] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports complete protection of rhesus macaques given an intramuscular VRP prime plus Env-protein boost, supporting the nonhuman-primate portion attributed to this source. It also says none of the macaques given VRP alone were protected, so the unqualified description of VRPs as potent vaccines overstates this study. The separate mice and humans citations are not being judged here. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [25] 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.
It may state two separate claims as one.
- Supported
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
“There are limited published data on the in vivo delivery of self-amplifying RNA using nonviral delivery strategies (3,14,18), and none has taken advantage of the recently developed, clinically suitable delivery systems for siRNA (19,20).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Supportedcites [14] source
This paper is cited for the first clause: examples of in vivo, nonviral delivery of self-amplifying RNA. The Discussion describes delivery of naked Semliki Forest virus RNA replicons and reports immune responses after intradermal delivery with electroporation. The separate claim about siRNA delivery systems is attached to other citations, not this paper. (LLM, conf=0.90)
- Not matchedcites [18]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [19] source
- Supportedcites [20] source
The Main section (page unavailable) describes synthetic, nonviral siRNA delivery systems that have worked in vivo and says several clinical trials use delivery agents. This supports the cited description of clinically promising siRNA delivery systems; the statement that self-amplifying RNA studies had not used them is the citing authors’ comparison, not a finding attributed to this source. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
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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
“Injection of naked mRNA or self-amplifying RNA in vivo induces gene expression and generates immune responses (4, 11-13), with self-amplifying RNA being more efficient for gene expression in situ (13,14).”
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [11] source
- Not checked — no full text of the sourcecites [12] source
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The in vivo gene-expression results report that injected replicative mRNA produced substantially more luciferase than non-replicative mRNA in muscle. The Discussion reports an immune response from prior CEA mRNA injections, but this study did not establish that its self-amplifying RNA generated an immune response; it discusses that possibility as a hypothesis (page not provided). (LLM, conf=0.87)
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Results section ('Relative expression levels and cellular immune response'; page unavailable) reports in vivo gene expression from both mRNA and replicon RNA, with lower, shorter-lived expression from mRNA. Replicon RNA elicited immune responses, but naked mRNA produced no detectable specific immune response in this study's single-injection experiments. The Introduction does report immune responses to mRNA vaccination in other studies, so the broad claim is supported only with that qualification. (LLM, conf=0.86)
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.
- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“The F protein of RSV is a conserved target of neutralizing antibodies and a promising antigen for RSV vaccine development (29).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Supportedcites [29] source
The introductory passage following the Abstract explicitly calls RSV F “a conserved target of neutralizing antibodies” and “a promising antigen for RSV candidate vaccines.” The Discussion further reports that an engineered F antigen elicited high neutralizing antibody titers and protected cotton rats from RSV challenge. (LLM, conf=0.95)
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.
- Supported
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
“The neutralization titers elicited by LNP/RNA are above the titer of 380 that correlates with protection in cotton rats (30) and similar to passively acquired serum neutralizing titers that correlate with protection of human infants from severe RSV disease (31,32).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Currently there is no vaccine for RSV and, because of a history of disease enhancement upon natural infection after immunization with an RSV vaccine candidate that elicited T H 2-biased (and non-neutralizing) RSV-specific immune responses in RSV-naive infants, elicitation of a non-T H 2-biased RSV-specific response is considered an essential attribute for infant RSV vaccine candidates (33).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Partly supportedcites [33] sourceExperimental — accuracy not yet measured
The Major hurdles section says adequate RSV vaccine options were unavailable and describes enhanced disease in infants after the formalin-inactivated vaccine. The Vaccine-enhanced disease section reports poor neutralizing antibody responses in those children, and the Role of T cells in vaccine-enhanced illness section recommends avoiding Th2 responses in RSV vaccines. However, it identifies clear Th2 induction in immunized animal models, not as a directly established response in the infants; their lung eosinophilia is cited as a reason for concern. (LLM, conf=0.86)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The shorter duration of expression in situ after RNA immunization compared with pDNA may be related to the induction of apoptosis of the transfected cell, which could occur during RNA amplification, leading to transient gene expression (12,13).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [12] source
- Partly supportedcites [13] sourceExperimental — accuracy not yet measured
The in vivo results report that replicative mRNA expression returned to baseline within 28 days, while plasmid DNA expression remained above baseline (Augmented gene expression in vivo). The Discussion proposes host-cell protein-synthesis inhibition and resulting cytopathogenicity as one possible explanation for the decline in mRNA-directed expression. It does not specifically identify apoptosis or establish that it occurs during RNA amplification. (LLM, conf=0.85)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, there has been an exponential growth in the development of clinically suitable nonviral delivery systems for siRNA (19,20); we have taken advantage of these innovations to develop the LNP/RNA formulation and have now embarked on a more extensive evaluation of other nonviral delivery systems.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [19] source
- Partly supportedcites [20] sourceExperimental — accuracy not yet measured
The Main section describes advances in synthetic nonviral siRNA carriers and reports that some delivery agents are being used in clinical trials. It does not establish exponential growth, and it says safe, effective delivery remains a barrier rather than characterizing these systems generally as clinically suitable. Page numbers were not provided in our copy. (LLM, conf=0.85)
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 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 self-amplifying RNA, when delivered using a VRP (1 × 10 6 IU), produced twice the bioluminescence at day 3 compared with LNP/RNA, but expression decayed much more rapidly and reached background levels by day 28 (Fig. 2B).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
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
“EP delivery of pDNA (at a high dose of 20 μg) elicited anti-F IgG titers (GMTs of 6,712) on average 3.9-fold less than those elicited by 0.1 μg of LNP/RNA, although not statistically different.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
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
“On the other hand, mice administered a pDNA-encoding luciferase (10 μg) delivered using EP in situ displayed the highest measurable bioluminescence at all time points tested, and this level remained high for at least 63 d (Fig. 2D).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
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.
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
“Encapsulation of a 10-fold lower dose of RNA (0.1 μg) in LNPs increased the serum SEAP concentration and reduced the variability between animals.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
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
“Six days after intramuscular (i.m.) injection of 1 μg naked self-amplifying RNA encoding secreted alkaline phosphatase (SEAP), gene expression, as determined by serum SEAP concentration, was measurable but highly variable (Fig. 1D).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
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
“This contrasted with what was observed for naked RNA, which required two vaccinations and microgram doses of RNA.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
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
“The LNP/RNA was statistically superior to naked RNA and equivalent to the 5 ×10 6 IU of VRPs [GMTs 5,861 (F-specific IgG) and 1,690 (neutralization)].”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
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
“Addition of empty LNPs (without RNA) to naked RNA (0.1 μg) decreased the serum SEAP concentration relative to LNP-encapsulated RNA, indicating that RNA encapsulation was necessary for efficient RNA delivery and reporter gene expression.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
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.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“A recombinant F protein subunit vaccine formulated with alum was shown to be the most potent vaccine for induction of total and protective antibody responses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no 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
“Bioluminescence intensity induced by LNP/RNA was substantially greater than naked RNA, pDNA, and pDNA launched RNA, and was comparable to the bioluminescence produced by 1 × 10 6 infectious units (IU) of VRPs.”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
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
“Agarose gel electrophoresis showed that RNA integrity was maintained during formulation (Fig. 1C, lane 4) and that the LNPs protected the RNA from degradation by RNase A (Fig. 1C, lane 5).”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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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 an extended study (Fig. 2 B-D), mice injected with LNP/RNA (1 μg) showed measurable bioluminescence that was already high on day 3, peaked on day 7, and decreased to background by day 63 (Fig. 2C).”
§ Nonviral delivery of self-amplifying RNA vaccines > In Vivo Gene Expression at the Site of Injection.
plaindirect- Asserted: passes — The authors put it forward as true.
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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 potency of this unique LNP/RNA vaccine in mice and cotton rats was comparable to a single-cycle alphavirus vector (VRP, 1 × 10 6 IU) at a reasonable dose of RNA (1 μg) and was generally comparable to pDNA delivered using EP at higher doses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“All self-amplifying RNA vaccines provided protection from a nasal RSV challenge, reducing the lung viral load >1,000-fold compared with control animals (Fig. 5C) and these data are in agreement with previous reports for naked RNA (12).”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
What the sources say
- Not checked — no full text of the sourcecites [12] source
plaindirect- Asserted: passes — The authors put it forward as true.
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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 LNP/RNA formulation boosted F-specific IgG titers approximately 8-fold (GMTs 4,355) and neutralization titers 10-fold (GMTs 1,493) relative to the same dose of naked RNA [GMTs of 526 (F-specific IgG) and 154 (neutralization)].”
§ Nonviral delivery of self-amplifying RNA vaccines > Virus Fusion Glycoprotien (RSV-F).
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“An ethanol dilution process (28) was used to produce small uniform lipid particles with a high RNA encapsulation efficiency.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
What the sources say
- Not checked — no full text of the sourcecites [28] source
plaindirect- Asserted: passes — The authors put it forward as true.
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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 number-weighted mean diameters ranged from 79 to 121 nm and Z-average diameters from 130 to 164 nm with a polydispersity index from 0.09 to 0.14.”
§ Nonviral delivery of self-amplifying RNA vaccines > Vaccine Formulation Characterization.
plain- Asserted: passes — The authors put it forward as true.
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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 ratio of F-specific IgG titer to RSV neutralization titer (Table S2) is low for the LNP/ RNA vaccine relative to the RSV-F subunit adsorbed on alum; thus it may be particularly suitable for development into a safe and effective infant RSV vaccine candidate.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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 LNP/RNA provides this benefit (Fig. 4) in addition to strong cellular immune responses.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“(iv) the generation of a humoral and cellular immune responses (both CD4 and CD8).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Facilitated delivery of RNA, either by VRPs or LNPs, resulted in higher levels of reporter gene expression (SEAP and luciferase) than naked RNA delivery and considerably lower variability of expression between animals.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“However, many of the obstacles to mRNA vaccine development have been surmounted, and recently there has been a revival in the use of nonamplifying mRNA vaccines for cancer (6), allergy (7), and gene therapy (8).”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“Naturally transient and cytosolically active mRNA can now be produced at sufficient quantity and quality for human clinical trials (6) and is seen by many (9) as a safer and more potent alternative to pDNA for vaccination.”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Viral vector-based technologies are generally regarded as the most efficient means to deliver nucleic acids into cells, but their utility can be restricted by preexisting or vaccine-induced antivector immunity that can decrease vaccine potency (12).”
What the sources say
- Not checked — no full text of the sourcecites [12] source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Recombinant viral vector technologies have the advantage of efficient delivery of the nucleic acid payload, but their utility is often hampered by antivector immunity, production limitations, and safety concerns (3,4).”
What the sources say
- Not checked — no full text of the sourcecites [3] source
- Not checked — no full text of the sourcecites [4]
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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Various RNA vaccines have been evaluated in human clinical trials, including naked and formulated non-amplifying mRNA (37-39) and self-amplifying RNA packaged in VRPs (25).”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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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
“RNA vaccines avoid this rate-limiting step by using cytoplasmic amplification and expression, resulting in more efficient transfection of different cell types, including quiescent or slowly proliferating cells, such as vascular endothelia or myocytes.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Therefore, the LNP formulation markedly enhances the potency of the self-amplifying RNA, thereby generating a robust and potentially generic vaccine technology.”
§ Nonviral delivery of self-amplifying RNA vaccines > 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.
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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
“Image acquisition times were kept constant as bioluminescence was measured with a cooled CCD camera.”
§ Nonviral delivery of self-amplifying RNA vaccines > RNA Synthesis.
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Those studies showed RNA vaccines to be well tolerated and immunogenic.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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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
“In addition, because the replication cycle of the self-amplifying RNA is strictly cytoplasmic, the need for codon modification is diminished, and the risks of splicing and destruction of the transcript are avoided.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. 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
“For an LNP/RNA vaccine, this sequestration might result in antigen production and/or stimulation of innate immune pathways within these immune cells.”
§ Nonviral delivery of self-amplifying RNA vaccines > 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“(ii) elimination of theoretical risks of generating infectious virus through recombination during production”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no 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
“The LNP delivery system may achieve these effects by a combination of increased transfection efficiency and protection of the RNA from enzymatic degradation at the site of injection.”
§ Nonviral delivery of self-amplifying RNA vaccines > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- 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 paper relies on this without support.
There is still no commercial product for human use for nucleic acid vaccines despite more than two decades of research and development.
“Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use.”
The paper relies on this without support.
mRNA-based vaccines must match the potency of viral vectors at doses of RNA that are not cost prohibitive to be commercially competitive as a platform technology.
“However, to be commercially competitive as a platform technology, mRNA-based vaccines must match the potency of viral vectors at doses of RNA that are not cost prohibitive.”
The paper relies on this without support.
The major limitation for delivery of pDNA is the nuclear barrier, and transport across the nuclear membrane is particularly inefficient in nondividing cells such as mature myocytes.
“The major limitation for delivery of pDNA is thought to be the nuclear barrier, and transport across the nuclear membrane seems to be particularly inefficient in nondividing cells, such as mature myocytes.”
The paper relies on this without support.
The immunogenicity and protection observed in mice and cotton rats are predictive of efficacy in humans.
“Thus, this technology has potential as a platform to address multiple disease targets.”
The paper relies on this without support.
The SAM vaccine platform can be applied to multiple disease targets.
“Thus, this technology has potential as a platform to address multiple disease targets.”
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 cited source says what the claim attributes to it.
In the citing paper
“Studies with self-amplifying mRNA vaccines investigated the effect of different formulations such as lipid-nanoparticles (LNP)10 or cationic nanoemulsion (CNE)11 on the immunogenicity of mRNA vaccines. Self-amplifying vaccines benefited from formulation with LNP or CNE and were able to induce protective antibody titers.”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [10]
In the citing paper
“Decades later, Geall and colleagues were the first to use LNP to encapsulate a saRNA chimera composed of the Venezuelan equine encephalitis virus (VEEV) and Sindbis virus (SINV) replicons into a vaccine which was used to immunize mice, and immunogenicity was significantly improved compared with unencapsulated group.199”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [199]
In the citing paper
“Based on the potential toxicity of liposomes in clinical application,25,26 the success of the first approved small interfering RNA-lipid nanoparticle (LNP) therapeutic27 and mRNA COVID-19 vaccines originates only from their delivery using ionizable lipid-containing LNPs,28, 29, 30”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [30]
In the citing paper
“In preclinical studies, mRNA vaccines encoding either the native RSV F protein or the stabilized prefusion conformation were successfully delivered using cationic nanoemulsions109 and LNPs179,180 without any observed instances of VAED.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [180]
Citations
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BackgroundDNA vaccines: ready for prime time?
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Induction of virus‐specific cytotoxic T lymphocytes in vivo by liposome‐entrapped mRNA
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Vaccines for the twenty-first century society
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Self-citationWeide, B., Pascolo, S., Scheel, B., Derhovanessian, E., Pflugfelder, A., Eigentler, T. K., Pawelec, G., Hoerr, I., Rammensee, H.-G., & Garbe, C. (2009) · Journal of Immunotherapy · doi:10.1097/cji.0b013e3181a00068 · Cited by 378
Cited by
Sorted by citations
Items 201–300 of 673
Therapeutic mRNA delivery to leukocytes
Granot-Matok, Y., Kon, E., Dammes, N., Mechtinger, G., & Peer, D. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.05.032 · Cited by 64
Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus
Mukherjee, R. (2020) · Journal of Biosciences · doi:10.1007/s12038-020-00040-7 · Cited by 62
“The resulting virus can express the heterologous antigenic genes in the cytoplasm in high numbers but cannot package itself into a functional virus, while the mRNA can amplify itself using the RNA dependent RNA polymerase coded in its genome (Geall et al. 2012).”
BackgroundInvestigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines
Anderluzzi, G., Lou, G., Gallorini, S., Brazzoli, M., Johnson, R., O’Hagan, D. T., Baudner, B. C., & Perrie, Y. (2020) · Vaccines · doi:10.3390/vaccines8020212 · Cited by 57
“Co-formulation of SAM and lipid nanoparticles (LNPs) further supports increased vaccine potency, as LNPs augment in vivo stability by preserving the nucleic acid from enzymatic degradation and facilitating accumulation within cell cytosol [10].”
BackgroundMethodInfluentialSelf-citationProgress and challenges towards CRISPR/Cas clinical translation
Rosenblum, D., Gutkin, A., Dammes, N., & Peer, D. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.07.004 · Cited by 61
Development and applications of mRNA treatment based on lipid nanoparticles
Wang, Z., Ma, W., Fu, X., Qi, Y., Zhao, Y., & Zhang, S. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108130 · Cited by 57
Development of vaccines for SARS-CoV-2
Ng, W. H., Liu, X., & Mahalingam, S. (2020) · F1000Research · doi:10.12688/f1000research.25998.1 · Cited by 55
Greene, M. K., Johnston, M. C., & Scott, C. J. (2021) · Cancers · doi:10.3390/cancers13246175 · Cited by 59
Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Cu, Y., Broderick, K. E., Banerjee, K., Hickman, J., Otten, G. R., Barnett, S. W., Kichaev, G., Sardesai, N. Y., Ulmer, J. B., & Geall, A. J. (2013) · Vaccines · doi:10.3390/vaccines1030367 · Cited by 58
“The potency of naked mRNA vaccines can be enhanced by cationic molecules [21], or lipid particles [17,22,23].”
BackgroundSelf-citationRNActive® Technology: Generation and Testing of Stable and Immunogenic mRNA Vaccines
Rauch, S., Lutz, J., Kowalczyk, A., Schlake, T., & Heidenreich, R. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-6481-9_5 · Cited by 57
Nebulised delivery of RNA formulations to the lungs: From aerosol to cytosol
Neary, M. T., Mulder, L. M., Kowalski, P. S., MacLoughlin, R. J., Crean, A. M., & Ryan, K. B. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.012 · Cited by 63
Self-Amplifying RNA: A Second Revolution of mRNA Vaccines against COVID-19
Silva-Pilipich, N., Beloki, U., Salaberry, L., & Smerdou, C. (2024) · Vaccines · doi:10.3390/vaccines12030318 · Cited by 64
“The use of LNPs for the delivery saRNA vaccines has been evaluated extensively since the first attempt, published more than a decade ago [33].”
BackgroundToward a Human Vaccines Project
Koff, W. C., Gust, I. D., & Plotkin, S. A. (2014) · Nature Immunology · doi:10.1038/ni.2871 · Cited by 54
Luo, F., Zheng, L., Hu, Y., Liu, S., Wang, Y., Xiong, Z., Hu, X., & Tan, F. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00605 · Cited by 56
“R© Plasmid Mini Kit (OMEGA Bio-tek, USA) and stored at −20◦C. Prior to immunization, the plasmids were linearized and RNAs in vitro transcription were made by using MEGAScriptTM Kit (Ambion, USA) as described previously (Geall et al., 2012).”
BackgroundMethodResultInfluentialVaccination with Messenger RNA: A Promising Alternative to DNA Vaccination
Tombácz, I., Weissman, D., & Pardi, N. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0872-2_2 · Cited by 55
Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses
Stromberg, Z. R., Fischer, W., Bradfute, S. B., Kubicek-Sutherland, J. Z., & Hraber, P. (2020) · Vaccines · doi:10.3390/vaccines8020273 · Cited by 51
Cafferty, S. M., Haque, A. K. M. A., Vandierendonck, A., Weidensee, B., Plovyt, M., Stuchlíková, M., François, N., Valembois, S., Heyndríckx, L., Míchiels, J., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.04.014 · Cited by 56
Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells
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“Indeed, lower doses of saRNA are able to elicit greater antibody titers compared to higher doses of DNA [108].”
BackgroundmRNA vaccines: a new era in vaccine development
Chandra, S., Wilson, J. C., Good, D. M., & Wei, M. Q. (2024) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2024.043987 · Cited by 58
“…to elicit more effective neutralizing antibody responses in animals by single or double-dosage immunizations [43,77,79]. mRNA vaccines have provided considerable optimism because they have generated an immune response against bacterial and viral infectious agents in mouse models [83,85,93,120].”
BackgroundRaffaele, J., Loughney, J. W., & Rustandi, R. R. (2021) · Electrophoresis · doi:10.1002/elps.202100272 · Cited by 51
Huang, C., Duan, X., Wang, J., Tian, Q., Ren, Y., Chen, K., Zhang, Z., Li, Y., Feng, Y., Zhong, K., et al. (2022) · Advanced Science · doi:10.1002/advs.202205532 · Cited by 56
Shah, R. R., Dodd, S., Schaefer, M. E., Ugozzoli, M., Singh, M., Otten, G. R., Amiji, M. M., O’Hagan, D. T., & Brito, L. A. (2015) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.24337 · Cited by 52
Self-citationDesign Strategies for and Stability of mRNA–Lipid Nanoparticle COVID-19 Vaccines
Liu, T., Tian, Y., Zheng, A., & Cui, C. (2022) · Polymers · doi:10.3390/polym14194195 · Cited by 54
“Mice Novartis Vaccines and Diagnostics [20]”
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Goswami, R., O’Hagan, D. T., Adamo, R., & Baudner, B. C. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13020240 · Cited by 50
“SAM promotes RNA amplification and requires lower dose compared to conventional mRNA vaccines [31,32].”
BackgroundMethodSelf-citationAn Update on mRNA-Based Viral Vaccines
Jeeva, S., Kim, K., Shin, C. H., Wang, B., & Kang, S. (2021) · Vaccines · doi:10.3390/vaccines9090965 · Cited by 49
“The efficacy of delivering mRNAs and immune responses is comparable to a viral vector containing the same gene [93].”
BackgroundMicroemulsion Based Nanostructures for Drug Delivery
Arredondo-Ochoa, T., & Silva-Martínez, G. A. (2022) · Frontiers in Nanotechnology · doi:10.3389/fnano.2021.753947 · Cited by 55
“, 2020),which contain a synthetic SARS-CoV-2 mRNA inside a lipid-based nanocarrier to achieve a high-efficient delivery into cells after intramuscular injection by the lipidic nature of the liposome allowing endosomal release of the mRNA into cytoplasm, increase the half-life of mRNA and the latter, lead to a prolonge…”
BackgroundRNA Replicon Delivery via Lipid-Complexed PRINT Protein Particles
Xu, J., Luft, J. C., Yi, X., Tian, S., Owens, G., Wang, J., Johnson, A. R., Berglund, P., Smith, J., Napier, M. E., et al. (2013) · Molecular Pharmaceutics · doi:10.1021/mp400190z · Cited by 51
Synthetic biology devices and circuits for RNA-based ‘smart vaccines’: a propositional review
Andries, O., Kitada, T., Bodner, K., Sanders, N. N., & Weiss, R. (2015) · Expert Review of Vaccines · doi:10.1586/14760584.2015.997714 · Cited by 50
“recently showed that gene expression from alphaviral RNA replicons can last for at least 7 weeks in vivo when replicon RNA was packaged in lipid nanoparticles and injected into the muscle of mice for vaccination [44].”
BackgroundZhong, Z., McCafferty, S., Opsomer, L., Wang, H., Huysmans, H., De Temmerman, J., Lienenklaus, S., Portela Catani, J. P., Combes, F., & Sanders, N. N. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.01.023 · Cited by 48
“DISCUSSION Synthetic sa-mRNAs are known for their high in vivo translation efficiency.(23,24) However, in vivo administration of sa-mRNAs may induce a strong type I IFN response.”
BackgroundNext generation self-replicating RNA vectors for vaccines and immunotherapies
Aliahmad, P., Miyake-Stoner, S. J., Geall, A. J., & Wang, N. S. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00435-8 · Cited by 50
“Indeed, the first report of any fully synthetic RNA vaccine delivered in vivo in a LNP-based formulation was a VEEV replicon [23].”
BackgroundSelf-citationAdvances in the design and delivery of RNA vaccines for infectious diseases
Lokras, A. G., Bobak, T. R., Baghel, S. S., Sebastiani, F., & Foged, C. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115419 · Cited by 52
Blakney, A. K., McKay, P. F., Christensen, D., Yus, B. I., Aldon, Y., Follmann, F., & Shattock, R. J. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.04.043 · Cited by 48
Nanomaterials for direct and indirect immunomodulation: A review of applications
Kubackova, J., Zbytovská, J., & Holas, O. (2019) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2019.105139 · Cited by 48
Structural components for amplification of positive and negative strand VEEV splitzicons
Blakney, A. K., McKay, P. F., & Shattock, R. J. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00071 · Cited by 47
Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery
Haque, M. A., Shrestha, A., Mikelis, C. M., & Mattheolabakis, G. (2024) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2024.100283 · Cited by 52
“Briefly, representative examples include 1 – 100 mM citrate buffer at pH 3 – 6 (Alabi et al., 2013; ´ et al., 2022; Billingsley et al., 2020; Geall et al., 2012; Larson et al., 2022; Naderi Sohi et al., 2021; Patel et al., 2017; Prakash et al., 2013; Zhang et al., 2021a), 20 – 50 mM acetate buffer…”
BackgroundAyad, C., Libeau, P., Lacroix, C., Ladavière, C., & Verrier, B. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13030377 · Cited by 48
“In addition to a charged or ionizable lipid, LNP formulations typically include cholesterol, phospholipids and polyethylene glycol-lipids (PEG-lipids) [5,14] such as DMG-PEG 2000 [21] or C14-PEG 2000 [22].”
BackgroundMessenger RNA-Based Therapeutics and Vaccines: What’s beyond COVID-19?
Li, D., Liu, C., Li, Y., Tenchov, R., Sasso, J. M., Zhang, D., Li, D., Zou, L., Wang, X., & Zhou, Q. A. (2023) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.3c00047 · Cited by 50
Cancer Nanovaccines: Mechanisms, Design Principles, and Clinical Translation
Zaccariotto, G. D. C., Bistaffa, M. J., Zapata, A. M. M., Rodero, C. F., Coelho, F. M., Quitiba, J. V. B., de Lima, L. L. P., Sterman, R. G., Cardoso, V. M. D. O., & Zucolotto, V. (2025) · ACS Nano · doi:10.1021/acsnano.4c15765 · Cited by 54
Lybaert, L., Vermaelen, K. Y., Geest, B. G. D., & Nuhn, L. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.09.009 · Cited by 46
Improving Cancer Vaccine Efficiency by Nanomedicine
Cai, J., Wang, H., Wang, D., & Li, Y. (2019) · Advanced Biosystems · doi:10.1002/adbi.201800287 · Cited by 44
Vaccines ‘on demand’: science fiction or a future reality
Ulmer, J. B., Mansoura, M. K., & Geall, A. J. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.996128 · Cited by 45
“Initial preclinical testing of self-amplifying mRNA vaccines has shown non-viral delivery to be capable of producing potent and robust innate and adaptive immune responses in various animal species, including non-human primates (NHPs) [4,13-16].”
InfluentialSelf-citationSelf-amplifying mRNA-Based Vaccine Technology and Its Mode of Action
Maruggi, G., Ulmer, J. B., Rappuoli, R., & Yu, D. L. (2021) · Current topics in microbiology and immunology · doi:10.1007/82_2021_233 · Cited by 46
Self-citationPandemic-response adenoviral vector and RNA vaccine manufacturing
Kis, Z., Tak, K., Ibrahim, D., Papathanasiou, M. M., Chachuat, B., Shah, N., & Kontoravdi, C. (2022) · npj Vaccines · doi:10.1038/s41541-022-00447-3 · Cited by 52
Takanashi, A., Pouton, C. W., & Al-Wassiti, H. A. (2023) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c01024 · Cited by 48
Morphological Characterization of Self-Amplifying mRNA Lipid Nanoparticles
Thelen, J. L., Leite, W. C., Urban, V. S., O’Neill, H., Grishaev, A., Curtis, J. E., Krueger, S., & Castellanos, M. M. (2024) · ACS Nano · doi:10.1021/acsnano.3c08014 · Cited by 45
Maine, C. J., Miyake-Stoner, S. J., Spasova, D. S., Picarda, G. G. A., Chou, A. C., Brand, E. D., Olesiuk, M. D., Domingo, C. C., Little, H. J., Goodman, T. T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-55843-9 · Cited by 55
“An additional strength of srRNA technology is its ability to elicit cellular immunity 30,43 – 45 .”
Self-citationControl of alphavirus-based gene expression using engineered riboswitches
Bell, C. L., Yu, D. L., Smolke, C. D., Geall, A. J., Beard, C. W., & Mason, P. W. (2015) · Virology · doi:10.1016/j.virol.2015.04.023 · Cited by 44
Self-citationEftekhari, Z., Zohrabi, H., Oghalaie, A., Ebrahimi, T., Shariati, F. S., Behdani, M., & Kazemi‐Lomedasht, F. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102313 · Cited by 46
Shaw, C. A., Ciarlet, M., Cooper, B. W., Dionigi, L., Keith, P., O'Brien, K. B., Rafie‐Kolpin, M., & Dormitzer, P. R. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.05.003 · Cited by 45
Self-citationPlant viral and bacteriophage delivery of nucleic acid therapeutics
Lam, P. M. W., & Steinmetz, N. F. (2017) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1487 · Cited by 45
Hoecke, L. V., Verbeke, R., Vlieger, D. D., Dewitte, H., Roose, K., Nevel, S. V., Krysko, O., Bachert, C., Schepens, B., Lentacker, I., et al. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.04.015 · Cited by 46
“A number of nanoparticle carriers(34,35) have been proposed to increase the delivery efficiency of mRNA, protecting the mRNA against degradation by ubiquitous RNases and assisting in transfection of the intended target cells.(36,37) Here, mRNA encoding bi-specific VHH fusion proteins were formulated into DOTAP/cholest…”
BackgroundPalmer, C. D., Scallan, C. D., Kraemer Tardif, L. D., Kachura, M. A., Rappaport, A. R., Koralek, D. O., Uriel, A., Gitlin, L., Klein, J., Davis, M. J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39053-9 · Cited by 42
“The amplifying nature of samRNA vaccines generates high and durable transgene expression compared to mRNA vaccines 21 , thereby driving high nAb titers in mice 22,23 for a long period of time at low doses, suggesting that this platform can be dose-sparing 20 .”
Respiratory Syncytial Virus Vaccines: An update on those in the Immediate Pipeline
Esposito, S., & Pietro, G. M. D. (2016) · Future Microbiology · doi:10.2217/fmb-2016-0106 · Cited by 41
Zhang, W., Pfeifle, A., Lansdell, C., Frahm, G. E., Cecillon, J., Tamming, L. A., Gravel, C., Gao, J., Raman, S. N. T., Wang, L., et al. (2023) · Vaccines · doi:10.3390/vaccines11101580 · Cited by 45
“Nucleic acid detected in wells without triton was considered unencapsulated, while nucleic acid detected in wells where triton was added to disrupt the LNP represented total nucleic acid.”
BackgroundBathula, N. V., Friesen, J. J., Casmil, I. C., Wayne, C. J., Liao, S., Soriano, S. K. V., Ho, C.-H., Strumpel, A., & Blakney, A. K. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.07.078 · Cited by 44
de Oliveira, B. C., Duthie, M. S., & Pereira, V. R. A. (2019) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2019.1678998 · Cited by 48
Lipid Nanoparticles Potentiate CpG-Oligodeoxynucleotide-Based Vaccine for Influenza Virus
Shirai, S., Shibuya, M., Kawai, A., Tamiya, S., Munakata, L., Omata, D., Suzuki, R., Aoshi, T., & Yoshioka, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2019.03018 · Cited by 45
Delivery of synthetic mRNAs for tissue regeneration
Steinle, H., Weber, M., Stoppelkamp, S., Große‐Berkenbusch, K., Golombek, S., Weber, M., Çanak-Ipek, T., Trenz, S.-M., Schlensak, C., & Avci‐Adali, M. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114007 · Cited by 42
The Development of mRNA Vaccines for Infectious Diseases: Recent Updates
Nitika, Wei, J., & Hui, A. (2021) · Infection and Drug Resistance · doi:10.2147/idr.s341694 · Cited by 42
“mRNA vaccines are much safer than other vaccine platforms and hold promise to be effective against infectious pathogens.(13,15,20,23,24)”
BackgroundPorcine Epidemic Diarrhea: Insights and Progress on Vaccines
Park, J.-E. (2024) · Vaccines · doi:10.3390/vaccines12020212 · Cited by 42
“Self-amplifying RNA (saRNA) vaccines, which are developed via the incorporation of alphavirus replicase and viral genes, replicate RNA in the cytoplasm [141,142].”
BackgroundVaccine design: emerging concepts and renewed optimism
Grimm, S. K., & Ackerman, M. E. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2013.02.015 · Cited by 41
“VLPs, liposomes, DNA vaccines, and viral vectors offer means to present antigens in relatively native formats, and these vectors and adjuvant systems can serve both to compensate for the lack of stimulatory co-signals in recombinant subunit vaccines, and to provide specific delivery and immune-modulatory capacities.”
BackgroundInfluentialMiller, J. B., & Siegwart, D. J. (2018) · Nano Research · doi:10.1007/s12274-018-2099-4 · Cited by 41
Delivery of nucleic acid therapeutics for cancer immunotherapy
Zhou, S., Chen, W., Cole, J., & Zhu, G. (2020) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2020.100023 · Cited by 42
Lofano, G., Mallett, C. P., Bertholet, S., & O’Hagan, D. T. (2020) · npj Vaccines · doi:10.1038/s41541-020-00238-8 · Cited by 41
Self-citationLundstrom, K. H. (2015) · Viruses · doi:10.3390/v7052321 · Cited by 40
Rissanou, A. N., Ouranidis, A., & Karatasos, K. (2020) · Soft Matter · doi:10.1039/d0sm00736f · Cited by 38
Self-Amplifying Replicon RNA Delivery to Dendritic Cells by Cationic Lipids
Englezou, P. C., Sapet, C., Démoulins, T., Milona, P., Ebensen, T., Schulze, K., GUZMAN, C., Poulhès, F., Zelphati, O., Ruggli, N., et al. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.04.019 · Cited by 38
Model-Driven Engineering of Gene Expression from RNA Replicons
Beal, J., Wagner, T. E., Kitada, T., Azizgolshani, O., Parker, J. M., Densmore, D., & Weiss, R. (2015) · ACS Synthetic Biology · doi:10.1021/sb500173f · Cited by 38
Evaluating how cationic lipid affects mRNA-LNP physical properties and biodistribution
Guéguen, C., Chimol, T. B., Briand, M., Renaud, K., Seiler, M., Ziesel, M., Erbacher, P., & Hellal, M. (2023) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2023.08.002 · Cited by 39
DeFrancesco, L. (2017) · Nature Biotechnology · doi:10.1038/nbt.3812 · Cited by 40
Polylactide-Based Reactive Micelles as a Robust Platform for mRNA Delivery
Lacroix, C., Humanes, A., Coiffier, C., Gigmès, D., Verrier, B., & Trimaille, T. (2020) · Pharmaceutical Research · doi:10.1007/s11095-019-2749-6 · Cited by 41
Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era
Xu, C., Lei, C., Hosseinpour, S., Ivanovski, S., Walsh, L. J., & Khademhosseini, A. (2022) · National Science Review · doi:10.1093/nsr/nwac124 · Cited by 39
“Since nakedmRNA is not stable and is degraded readily by extracellular RNase enzymes, the lipid nanoparticle protects the mRNA during storage and after administration, and is essential for vaccine efficacy [29,30].”
BackgroundRapid Production of Synthetic Influenza Vaccines
Dormitzer, P. R. (2014) · Current topics in microbiology and immunology · doi:10.1007/82_2014_399 · Cited by 40
Self-citationRational design of lipid nanoparticles for enabling gene therapies
Brimacombe, C. A., Kulkarni, J. A., Cheng, M. H. Y., An, K., Witzigmann, D., & Cullis, P. R. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101518 · Cited by 45
“The first studies that established the potential of LNP RNA-based vaccines used self-amplifying RNA 192 in combination with LNP containing DLinDMA developed for delivery of siRNA to the liver.”
Recent Developments in Preclinical DNA Vaccination
Okuda, K., Wada, Y., & Shimada, M. (2014) · Vaccines · doi:10.3390/vaccines2010089 · Cited by 37
“Given the many positive attributes of nucleic acid vaccines, their results suggest that a comprehensive evaluation of non-viral technologies to deliver self-amplifying RNA vaccines is warranted [66].”
BackgroundEnhancing the Quality of Antibodies to HIV-1 Envelope by GagPol-Specific Th Cells
Bonsmann, M. S. G., Niezold, T., Temchura, V., Pissani, F., Ehrhardt, K., Brown, E. P., Osei‐Owusu, N. Y., Hannaman, D., Hengel, H., Ackerman, M. E., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501377 · Cited by 39
RNA-based therapy for osteogenesis
Wang, P., Perche, F., Logeart‐Avramoglou, D., & Pichon, C. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118594 · Cited by 38
CD8 + T cells mediate protection against Zika virus induced by an NS3-based vaccine
Ngono, A. E., Syed, T., Nguyen, A.-V. T., Regla-Nava, J. Á., Susantono, M., Spasova, D. S., Aguilar, A., West, M., Sparks, J., Gonzalez, A., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb2154 · Cited by 36
Blakney, A. K., Abdouni, Y., Yilmaz, G., Liu, R., McKay, P. F., Bouton, C. R., Shattock, R. J., & Becer, C. R. (2020) · Biomacromolecules · doi:10.1021/acs.biomac.0c00445 · Cited by 36
mRNA delivery via non-viral carriers for biomedical applications
Shuai, Q., Zhu, F., Zhao, M., & Yan, Y. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.121020 · Cited by 35
Demystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases
Rouf, N. Z., Biswas, S., Tarannum, N., Oishee, L. M., & Muna, M. M. (2022) · RNA Biology · doi:10.1080/15476286.2022.2055923 · Cited by 39
“Respiratory syncytial virus infection Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection among infants and elderly individuals and it is responsible for approximately 74,000 deaths per year [201,202].”
BackgroundMethodInfluentialNanoformulations targeting immune cells for cancer therapy: mRNA therapeutics
Yang, W., Cao, J., Cheng, H., Chen, L., Yu, M., Chen, Y., & Cui, X. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.11.014 · Cited by 36
“Now, solid LNPs that were first explored in delivering self-amplifying mRNA vaccines in 2012 [104], are favourably used in clinic.”
Antiviral Regulation in Porcine Monocytic Cells at Different Activation States
Sang, Y., Rowland, R. R. R., & Blecha, F. (2014) · Journal of Virology · doi:10.1128/jvi.01714-14 · Cited by 36
“Our efforts now will be to introduce a modified lipid nanoparticle (LNP) procedure (59) to deliver both ToFA (as an adjuvant) and the PRRSV-IFN construct as a vaccine platform in pigs to further validate the vaccine effect of ToFA and the PRRSV-IFN expression construct in vivo.”
BackgroundMohammadi, Y., Nezafat, N., Negahdaripour, M., Eskandari, S., & Zamani, M. (2022) · Immunologic Research · doi:10.1007/s12026-022-09351-3 · Cited by 38
Design-of-experiments in vitro transcription yield optimization of self-amplifying RNA
Samnuan, K., Blakney, A. K., McKay, P. F., & Shattock, R. J. (2022) · F1000Research · doi:10.12688/f1000research.75677.1 · Cited by 36
Cancer vaccine strategies using self-replicating RNA viral platforms
Dailey, G. P., Crosby, E. J., & Hartman, Z. C. (2022) · Cancer Gene Therapy · doi:10.1038/s41417-022-00499-6 · Cited by 36
Phua, K. K. L. (2015) · Journal of Immunology Research · doi:10.1155/2015/680620 · Cited by 35
“They include the optimization of the mRNAmolecular structure [6, 7], direct in vivo administration of mRNA [8, 9], delivery routes [3, 4], evaluation of rationally designed gene carriers [10–14], and, recently, self-replicating RNA [15].”
BackgroundWang, D., Phan, S. I., DiStefano, D. J., Citron, M. P., Callahan, C., Indrawati, L., Dubey, S. A., Heidecker, G. J., Govindarajan, D., Liang, X., et al. (2017) · Journal of Virology · doi:10.1128/jvi.00066-17 · Cited by 35
“Among vaccine modalities developed to date are live attenuated vaccines (12), replication-competent or replication-defective viral vector vaccines (13), nucleic acid vaccines (14, 15), virosomes (16–19), nanoparticle vaccines (20), virus-like particles, and subunit vaccines (21–23).”
BackgroundImmunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA
Aldon, Y., McKay, P. F., Herrero, J. M., Vogel, A. B., Lévai, R. F., Maisonnasse, P., Dereuddre‐Bosquet, N., Haas, H., Fábián, K., Grand, R. L., et al. (2021) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2021.06.008 · Cited by 34
“Self-amplifying mRNA (saRNA or replicon) represents a promising mRNA vaccine strategy, developed to support high and longer-term expression of the GOI in contrast to non-replicating mRNA platforms, which cannot self-replicate to amplify the mRNA pool available for translation.(11) saRNAs are derived from single-strand…”
BackgroundRNA secondary structure packages evaluated and improved by high-throughput experimentsPreprint
Wayment-Steele, H. K., Kladwang, W., Strom, A. I., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.29.124511 · Cited by 34
Self-amplifying RNA COVID-19 vaccine
Wayne, C. J., & Blakney, A. K. (2024) · Cell · doi:10.1016/j.cell.2024.03.018 · Cited by 33
Cationic Nanostructures for Vaccines Design
Carmona‐Ribeiro, A. M., & Pérez-Betancourt, Y. (2020) · Biomimetics · doi:10.3390/biomimetics5030032 · Cited by 33
“Figure 6 shows the encapsulation of self-amplifying RNA based on alphavirus genome, which contains the genes encoding the alphavirus RNA replication machinery but lacks the genes encoding the viral structural proteins required for infection; the cationic liposome composition is also shown on the right as reproduced wi…”
MethodSimnani, F. Z., Singh, D., & Kaur, R. (2021) · 3 Biotech · doi:10.1007/s13205-021-03076-0 · Cited by 35
“2012), and non-viral delivery of self-amplifying RNA vaccine (Geall et al. 2012).”
BackgroundDissociation of skeletal muscle for flow cytometric characterization of immune cells in macaques
Liang, F., Ploquin, A., Hernández, J. D., Fausther‐Bovendo, H., Lindgren, G., Stanley, D. A., Salvador, A., Brenchley, J. M., Koup, R. A., Loré, K., et al. (2015) · Journal of Immunological Methods · doi:10.1016/j.jim.2015.06.011 · Cited by 35
“…muscle tissue at 72 h after vaccine administration based on the result of prior mouse studies where significant immune cell infiltration and antigen expression in response to potent vaccine adjuvants were found around this time point (Calabro et al., 2011; Mosca et al., 2008; Geall et al., 2012).”
BackgroundMethodSelf-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles
McCullough, K. C., Milona, P., Thomann, L., Démoulins, T., Englezou, P. C., Suter, R., & Ruggli, N. (2014) · Vaccines · doi:10.3390/vaccines2040735 · Cited by 35
“Current alphavirus replicon vaccines are capped using, for example, the Vaccinia Capping system [83].”
BackgroundMethodInfluentialSei, S., Ahadova, A., Keskin, D. B., Bohaumilitzky, L., Gebert, J. F., Doeberitz, M. V. K., Lipkin, S. M., & Kloor, M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1147590 · Cited by 36
Brief Comparison of the Efficacy of Cationic and Anionic Liposomes as Nonviral Delivery Systems
Ochoa-Sánchez, C., Rodríguez-León, E., Iñiguez-Palomares, R. A., & Rodríguez-Beas, C. (2024) · ACS Omega · doi:10.1021/acsomega.4c06714 · Cited by 35
Anti-COVID-19 Nanomaterials: Directions to Improve Prevention, Diagnosis, and Treatment
Souri, M., Chiani, M., Farhangi, A. A., Mehrabi, M. R., Nourouzian, D., Raahemifar, K., & Soltani, M. (2022) · Nanomaterials · doi:10.3390/nano12050783 · Cited by 34
“Extracellular RNases can degrade naked mRNAs, so it is necessary to encapsulate naked mRNAs [135,136].”
BackgroundLipid-Based Delivery Systems in Development of Genetic and Subunit Vaccines
Bolhassani, A. (2022) · Molecular Biotechnology · doi:10.1007/s12033-022-00624-8 · Cited by 36
Bioinspired Spatiotemporal Management toward RNA Therapies
Ma, Y., Li, S., Lin, X., & Chen, Y. (2023) · ACS Nano · doi:10.1021/acsnano.3c08219 · Cited by 32
Metadata
- Authors
- Geall, A. J., Verma, A., Otten, G. R., Shaw, C. A., Hekele, A., Banerjee, K., Cu, Y., Beard, C. W., Brito, L. A., Krucker, T., O’Hagan, D. T., Singh, M., Mason, P. W., Valiante, N. M., Dormitzer, P. R., Barnett, S. W., Rappuoli, R., Ulmer, J. B., & Mandl, C. W.
- Affiliations
- Novartis Vaccines and Diagnostics, Cambridge, MA 02139; and
- Novartis Institutes for BioMedical Research, Cambridge MA 02139
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-08-20
- Volume
- 109
- Issue
- 36
- Pages
- 14604-14609
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3437863
- OpenAlex
- W2051665875
- Cited by
- 675
- References
- 41
- Citations by year
- 2026: 34 · 2025: 63 · 2024: 66 · 2023: 66 · 2022: 79 · 2021: 78 · 2020: 74 · 2019: 41 · 2018: 31 · 2017: 28 · 2016: 31 · 2015: 27 · 2014: 31 · 2013: 24 · 2012: 2
- FWCI
- 9.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (5P01 AI066287, P01AI066287)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- self-amplifying RNA vaccine, lipid nanoparticles, siRNA delivery, nucleic acid vaccines, immunogenicity, protective immune response
- MeSH terms
- Alphavirus, Analysis of Variance, Animals, Electrophoresis, Agar Gel, Escherichia coli, Female, Fluorescent Antibody Technique, Humans, Lipids, Drug Delivery Systems, Statistics, Nonparametric, Vaccines, DNA, RNA, Small Interfering, Rats, Nanoparticles
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 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (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 ›
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