Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis
Open accessAbstract
BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS: Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Ocular AAV treatments have caused permanent visual acuity loss after intraocular inflammation.
“ocular AAV therapies leading to a permanent reduction in visual acuity following intraocular inflammation (9–11)”
From Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses (2021) · cites this paper as [9]
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)
Experimental — accuracy not yet measuredClinical trials have reported AAV dose-dependent intraocular inflammation and persistent visual acuity loss after subretinal AAV despite prophylactic immunosuppression.
“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).”
From Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses (2021) · cites this paper as [9]
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)
Experimental — accuracy not yet measuredIn phase 1/2 dose-escalation trials for RPE65-associated LCA, choroideremia, and RPGR-associated X-linked retinitis pigmentosa, patients receiving higher doses of AAV presented with signs of retinal inflammation including vitritis, retinitis, and choroiditis.
“In the phase 1/2 dose-escalation trials for RPE65-associated LCA, choroideremia, and retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa, patients receiving higher doses of AAV have presented with various signs of retinal inflammation, including vitritis, retinitis, and choroiditis,2,6,7 implicating the presence of a cell-mediated immune response.”
From Characterizing the cellular immune response to subretinal AAV gene therapy in the murine retina (2021) · cites this paper as [2]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDose-dependent retinal inflammation (GTAU) has been observed in many retinal gene therapy trials, limiting vector dose and therapeutic efficacy.
“Despite the perceived low immunogenicity of AAV and relative immune privilege of the intraocular environment,8 dose-dependent retinal inflammation, or gene therapy-associated uveitis (GTAU), has been observed in many retinal gene therapy trials, which limits the vector dose and therapeutic efficacy.”
From Characterizing the cellular immune response to subretinal AAV gene therapy in the murine retina (2021) · cites this paper as [2]
The Results (Inflammatory and Immune Responses) report inflammation or immune responses in five of eight higher-dose participants and none of four lower-dose participants; the Discussion describes these as dose-limiting toxic effects. The paper reports one trial, however, and does not establish that inflammation occurred in many retinal gene therapy trials or generally limited therapeutic efficacy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDespite a 28-day oral corticosteroid therapy started 2 days before the first IVT, 70.7% of lenadogene nolparvovec-treated eyes developed some degree of intraocular inflammation versus 10.2% of placebo-treated eyes.
“Despite a 28-day oral corticosteroid therapy started 2 days before the first IVT, a regimen similar to that provided in several other clinical studies using IVT or sub-retinal AAV-based gene therapies,41–45 70.7% of lenadogene nolparvovec-treated eyes developed some degree of intraocular inflammation versus 10.2% of placebo-treated eyes.”
From Randomized trial of bilateral gene therapy injection for m.11778G&gt;A <i>MT-ND4</i> Leber optic neuropathy (2023) · cites this paper as [45]
The Methods—Intervention section describes subretinal AAV-based gene therapy, and the Results—Adverse Events section refers to oral glucocorticoid use. Those passages support citing this paper as an example of a related study, but our copy does not establish that its corticosteroid regimen was similar in duration or timing. The 70.7% and 10.2% figures appear after the citation and are not attributed to this source. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment.
“This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment.”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
In Results > Inflammatory and Immune Responses (page unavailable), inflammation was followed by a persistent loss of visual acuity in one participant and temporarily attenuated retinal-sensitivity gains in another. The paper does not establish that inflammation caused irreversible retinal-cell loss or reduced the long-term durability of treatment; it discusses macular thinning and later sensitivity decline without attributing either to inflammation. It does not address treatment cost. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIf uncontrolled, intraocular inflammation can lead to irreversible retinal structural damage and reduced visual function.
“The intraocular inflammation is dose-dependent and can sometimes last for months or even years following treatment, leading to irreversible retinal structural damage and reduced visual function if uncontrolled (Bainbridge et al., 2015).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results (Inflammatory and Immune Responses; page not provided) report that inflammation or immune responses occurred in five of eight higher-dose participants and none of four lower-dose participants. One participant’s mild uveitis was followed by macular pigmentary changes and a persistent 15-letter loss of visual acuity. The paper does not establish that uncontrolled inflammation caused irreversible retinal damage or that inflammation lasted months or years; the Discussion instead attributes macular thinning most likely to temporary retinal detachment. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe intraocular inflammation is dose-dependent.
“The intraocular inflammation is dose-dependent and can sometimes last for months or even years following treatment, leading to irreversible retinal structural damage and reduced visual function if uncontrolled (Bainbridge et al., 2015).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results (Inflammatory and Immune Responses; Adverse Events, page unavailable) report intraocular inflammation in three higher-dose participants and none in the lower-dose group, supporting a dose association. The paper describes the inflammation as mild or transient; it does not report inflammation lasting months or years or establish that uncontrolled inflammation causes irreversible retinal damage. It does report persistent visual-acuity loss and macular pigmentary changes after one episode of uveitis. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOne participant developed anterior uveitis at 2 weeks, followed by CRA and reduced visual acuity by 6 months.
“Notably, one participant developed anterior uveitis at 2 weeks, followed by CRA and reduced visual acuity by 6 months.”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results section (Inflammatory and Immune Responses; page unavailable) reports that Participant 7 had mild anterior uveitis followed by focal pigmentary changes at the macula and a persistent reduction in visual acuity. It does not identify those changes as CRA or give the claimed 2-week and 6-month timing. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTwo participants developed optic disc swelling, retinal vascular tortuosity/sheathing and mild vitritis.
“Two participants developed optic disc swelling, retinal vascular tortuosity/sheathing and mild vitritis.”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results section, “Inflammatory and Immune Responses” (page unavailable), reports that two participants (8 and 9) had episodes of posterior intraocular inflammation. Our copy does not specify optic disc swelling, retinal vascular tortuosity or sheathing, or mild vitritis in those participants. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThree out of eight participants who received the higher dose of vector (1 × 10^12 vg/eye) but none in the lower dose cohort (1 × 10^11 vg/eye) developed intraocular inflammation despite prophylactic peri-operative immunosuppression.
“Three out of eight participants who received the higher dose of vector (1 × 10 12 vg/eye) but none in the lower dose cohort (1 × 10 11 vg/eye) developed intraocular inflammation despite prophylactic peri-operative immunosuppression.”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Methods (Intervention) give the two dose levels and cohort sizes, while the Results (Adverse Events; Inflammatory and Immune Responses) report intraocular inflammation in three higher-dose participants and none in the lower-dose cohort. The Results mention oral glucocorticoids, but our copy does not establish that participants received prophylactic peri-operative immunosuppression. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGTAU is often diagnosed shortly after withdrawal of systemic immunosuppression prophylaxis or when the dose reaches around 15-20 mg for slower tapers, and sometimes several weeks to months after vector administration.
“Consequently, GTAU is often diagnosed shortly after the withdrawal of systemic immunosuppression prophy laxis (Dimopoulos et al., 2018) or when the dose reaches around 15 -20 mg for slower tapers, and sometimes several weeks to months after vector administration (Bainbridge et al., 2015).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results (Inflammatory and Immune Responses; Adverse Events, pages unavailable) report uveitis and other intraocular inflammation after vector administration. They do not establish that these episodes were diagnosed several weeks to months later or when an immunosuppression taper reached 15–20 mg; the week-4 finding concerns immune markers, not the date of uveitis diagnosis. The withdrawal clause is separately cited to Dimopoulos et al. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAAV vector-mediated retinal gene therapies have demonstrated efficacy in clinical trials for inherited retinal dystrophies.
“Although adeno-associated viral (AAV) vector-mediated retinal gene therapies have demonstrated efficacy”
From Characterizing the cellular immune response to subretinal AAV gene therapy in the murine retina (2021) · cites this paper as [2]
The intraocular inflammation can sometimes last for months or even years following treatment.
“The intraocular inflammation is dose-dependent and can sometimes last for months or even years following treatment, leading to irreversible retinal structural damage and reduced visual function if uncontrolled (Bainbridge et al., 2015).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Bainbridge et al., 2015
The Results (Adverse Events and Inflammatory and Immune Responses; page unavailable) report intraocular inflammation after treatment, describing it as mild or transient and referring to episodes. They do not state how long the inflammation lasted or establish that it could persist for months or years; searches for persistent inflammation and its duration found no such passage. (LLM, conf=0.73)
Experimental — accuracy not yet measuredIn phase I/II clinical trials for RPE65-LCA at University College London, ocular inflammation was noted following SRI of 1 × 10^12 vg of AAV2-RPE65.
“In phase I/II clinical trials for RPE65-LCA at University College London (ClinicalTrials.gov: NCT00643747), ocular inflammation was noted following SRI of 1 × 1012 vg of AAV2-RPE65.71,99”
From Current clinical applications of in vivo gene therapy with AAVs (2021) · cites this paper as [99]
Subfoveal viral gene therapy has been associated with various adverse effects, such as RPE alterations, retinal thinning, foveal morphological changes, vision loss, and variable duration of clinical effects.
“subfoveal viral gene therapy has been associated with various adverse effects, such as RPE alterations, retinal thinning, foveal morphological changes, vision loss, and the variable duration of clinical effects [281,294,296,297,298].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [296]
Dose-dependent immune responses have been observed, with high doses potentially leading to persistent inflammation and clinically significant vision loss in patients receiving high-dose AAV2 vector-based subretinal RPE65 therapy.
“Dose-dependent immune responses have also been observed, with high doses potentially leading to persistent inflammation and clinically significant vision loss in patients receiving high-dose AAV2 vector-based subretinal RPE65 therapy [296].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [296]
Some adverse events linked to glucocorticoids themselves have already been described in retinal rAAV trials, pointing out the need for other alternatives to mitigate inflammation.
“However, some adverse events linked to the glucocorticoids themselves have already been described in retinal rAAV trials which point out the need for other alternatives to mitigate the inflammation [37].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [37]
In an LCA trial (NCT00643747, Phase 1/2), retinal sensitivity improved, but final transgene expression in the high dose group was adversely affected by ocular inflammation or immune responses.
“The results showed that retinal sensitivity was improved; however, the final transgene expression in the participants from the high dose group was adversely affected by ocular inflammation or immune responses [48].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [48]
Inflammatory reactions to gene therapy in the eye have led to permanent vision loss for some patients.
“Nonetheless, inflammatory reactions to gene therapy in the eye have led to permanent vision loss for some patients7–9.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hartong, D. T., Berson, E. L., & Dryja, T. P. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69740-7 · Cited by 2,924 · see citing works
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · see citing works
Effect of gene therapy on visual function in Leber’s congenital amaurosis
Bainbridge, J. W. B., Smith, A. J., Barker, S. S., Robbie, S., Henderson, R., Balaggan, K., Viswanathan, A., Holder, G. E., Stockman, A., Tyler, N., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802268 · Cited by 1,924 · see citing works
Self-citationStatistics Notes: Measurement error
Bland, J. M., & Altman, D. G. (1996) · BMJ · doi:10.1136/bmj.313.7059.744 · Cited by 1,084 · see citing works
Hauswirth, W. W., Aleman, T. S., Kaushal, S., Cideciyan, A. V., Schwartz, S. B., Wang, L., Conlon, T. J., Boye, S. L., Flotte, T. R., Byrne, B. J., et al. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.107 · Cited by 954 · see citing works
Rpe65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle
Redmond., T. M., Yu, S., Lee, E., Bok, D., Hamasaki, D., Chen, N., Goletz, P., Ma, J.-X., Crouch, R. K., & Pfeifer, K. (1998) · Nature Genetics · doi:10.1038/3813 · Cited by 929 · see citing works
Maguire, A. M., High, K. A., Auricchio, A., Wright, J. F., Pierce, E. A., Testa, F., Mingozzi, F., Bennicelli, J. L., Ying, G.-S., Rossi, S., et al. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61836-5 · Cited by 865 · see citing works
Leber congenital amaurosis: Genes, proteins and disease mechanisms
den Hollander, A. I., Roepman, R., Koenekoop, R. K., & Cremers, F. P. M. (2008) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2008.05.003 · Cited by 811 · see citing works
Cideciyan, A. V., Alemán, T. S., Boye, S. L., Schwartz, S., Kaushal, S., Román, A. J., Pang, J., Sumaroka, A., Windsor, E. A. M., Wilson, J. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807027105 · Cited by 674 · see citing works
Jacobson, S. G. (2012) · Archives of Ophthalmology · doi:10.1001/archophthalmol.2011.298 · Cited by 639 · see citing works
Acland, G. M., Aguirre, G. K., Bennett, J., Alemán, T. S., Cideciyan, A. V., Bennicelli, J. L., Dejneka, N. S., Pearce-Kelling, S. E., Maguire, A. M., Palczewski, K., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.08.008 · Cited by 478 · see citing works
Cideciyan, A. V., Jacobson, S. G., Beltran, W. A., Sumaroka, A., Świder, M., Iwabe, S., Román, A. J., Olivares, M. B., Schwartz, S., Komáromy, A. M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218933110 · Cited by 441 · see citing works
Improvement and Decline in Vision with Gene Therapy in Childhood Blindness
Jacobson, S. G., Cideciyan, A. V., Román, A. J., Sumaroka, A., Schwartz, S., Héon, E., & Hauswirth, W. W. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412965 · Cited by 370 · see citing works
Testa, F., Maguire, A. M., Rossi, S., Pierce, E. A., Melillo, P., Marshall, K. A., Banfi, S., Surace, E. M., Sun, J., Acerra, C., et al. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2012.11.048 · Cited by 331 · see citing works
In Utero Gene Therapy Rescues Vision in a Murine Model of Congenital Blindness
Dejneka, N. S., Surace, E. M., Alemán, T. S., Cideciyan, A. V., Lyubarsky, A., Savchenko, A., Redmond, T. M., Tang, W., Wei, Z., Rex, T. S., et al. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.11.013 · Cited by 197 · see citing works
Schocket, L. S., Witkin, A. J., Fujimoto, J. G., Ko, T. H., Schuman, J. S., Rogers, A. H., Baumal, C. R., Reichel, E., & Duker, J. S. (2006) · Ophthalmology · doi:10.1016/j.ophtha.2006.01.003 · Cited by 147 · see citing works
FGFR1, signaling, and AP-1 expression after retinal detachment: reactive Müller and RPE cells.
Geller, S. F., Lewis, G. P., & Fisher, S. K. (2001) · PubMed · Cited by 141 · see citing works
Bemelmans, A., Kostic, C., Crippa, S. V., Hauswirth, W. W., Lem, J., Munier, F. L., Seeliger, M. W., Wenzel, A., & Arsenijévic, Y. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030347 · Cited by 118 · see citing works
Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina
Kaylor, J. J., Yuan, Q., Cook, J., Sarfare, S., Makshanoff, J., Miu, A., Kim, A., Kim, P., Habib, S., Roybal, C. N., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1114 · Cited by 107 · see citing works
Gene therapy in the second eye of RPE65-deficient dogs improves retinal function
Annear, M. J., Bartoe, J. T., Barker, S. E., Smith, A. J., Curran, P. G., Bainbridge, J. W., Ali, R. R., & Petersen‐Jones, S. M. (2010) · Gene Therapy · doi:10.1038/gt.2010.111 · Cited by 74 · see citing works
Self-citationBanin, E., Bandah‐Rozenfeld, D., Obolensky, A., Cideciyan, A. V., Alemán, T. S., Marks-Ohana, D., Sela, M. N., Boye, S. L., Sumaroka, A., Román, A. J., et al. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.047 · Cited by 69 · see citing works
RPE65 gene therapy slows cone loss in Rpe65-deficient dogs
Mowat, F. M., Breuwer, A. R., Bartoe, J. T., Annear, M. J., Zhang, Z., Smith, A. J., Bainbridge, J. W., Petersen‐Jones, S. M., & Ali, R. R. (2012) · Gene Therapy · doi:10.1038/gt.2012.63 · Cited by 65 · see citing works
Self-citationPredicting the pathogenicity ofRPE65mutations
Philp, A. R., Jin, M., Li, S., Schindler, E. I., Iannaccone, A., Lam, B. L., Weleber, R. G., Fishman, G. A., Jacobson, S. G., Mullins, R. F., et al. (2009) · Human Mutation · doi:10.1002/humu.21033 · Cited by 61 · see citing works
Self-citationKędzierski, W., Bok, D., & Travis, G. H. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-11-04076.1998 · Cited by 59 · see citing works
Li, S., Izumi, T., Hu, J. G., Jin, H. H., Siddiqui, A.-A. A., Jacobson, S. G., Bok, D., & Jin, M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.552117 · Cited by 41 · see citing works
Annear, M. J., Mowat, F. M., Bartoe, J. T., Querubin, J. R., Azam, S. A., Basche, M., Curran, P. G., Smith, A. J., Bainbridge, J. W., Ali, R. R., et al. (2013) · Human Gene Therapy · doi:10.1089/hum.2013.146 · Cited by 34 · see citing works
Self-citationAn alternative isomerohydrolase in the retinal Müller cells of a cone‐dominant species
Takahashi, Y., Moiseyev, G. P., Chen, Y., Nikolaeva, O., & Ma, J. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08216.x · Cited by 26 · see citing works
Poehner, W., Fossarello, M., Rapoport, A., Alemán, T. S., Cideciyan, A. V., Jacobson, S. G., Wright, A. F., Danciger, M., & Farber, D. B. (2000) · PubMed · Cited by 26 · see citing works
Regeneration of Photopigment Is Enhanced in Mouse Cone Photoreceptors Expressing RPE65 Protein
Tang, P. H., Wheless, L., & Crouch, R. K. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0182-11.2011 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Russell, 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 · see citing works
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410 · see citing works
The current landscape of nucleic acid therapeutics
Kulkarni, J. A., Witzigmann, D., Thomson, S. B., Chen, S., Leavitt, B. R., Cullis, P. R., & van der Meel, R. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00898-0 · Cited by 1,371 · see citing works
Gene therapy returns to centre stage
Naldini, L. (2015) · Nature · doi:10.1038/nature15818 · Cited by 1,184 · see citing works
Engineering adeno-associated virus vectors for gene therapy
Li, C., & Samulski, R. J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0205-4 · Cited by 1,175 · see citing works
Current clinical applications of in vivo gene therapy with AAVs
Mendell, J. R., Al-Zaidy, S. A., Rodino-Klapac, L. R., Goodspeed, K., Gray, S. J., Kay, C. N., Boye, S. L., Boye, S. E., George, L. A., Salabarria, S., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.007 · Cited by 743 · see citing works
Pharmacokinetic aspects of retinal drug delivery
del Amo, E. M., Rimpelä, A.-K., Heikkinen, E., Kari, O. K., Ramsay, E., Lajunen, T., Schmitt, M., Pelkonen, L., Bhattacharya, M., Richardson, D., et al. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.12.001 · Cited by 693 · see citing works
AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
Costa Verdera, H., Kuranda, K., & Mingozzi, F. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.12.010 · Cited by 641 · see citing works
Vitamin B <sub>3</sub> modulates mitochondrial vulnerability and prevents glaucoma in aged mice
Williams, P. A., Harder, J. M., Foxworth, N. E., Cochran, K. E., Philip, V. M., Porciatti, V., Smithies, O., & John, S. W. M. (2017) · Science · doi:10.1126/science.aal0092 · Cited by 617 · see citing works
High, K. A., & Roncarolo, M. G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1706910 · Cited by 555 · see citing works
Entering the Modern Era of Gene Therapy
Anguela, X. M., & High, K. A. (2018) · Annual Review of Medicine · doi:10.1146/annurev-med-012017-043332 · Cited by 474 · see citing works
Bennett, J., Wellman, J., Marshall, K. A., McCague, S., Ashtari, M., DiStefano-Pappas, J., Elci, O. U., Chung, D. C., Sun, J., Wright, J. F., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30371-3 · Cited by 461 · see citing works
Dias, M. F., Joo, K., Kemp, J. A., Fialho, S. L., Silva‐Cunha, A., Woo, S. J., & Kwon, Y. J. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.10.004 · Cited by 420 · see citing works
Maguire, A. M., Russell, S., Wellman, J. A., Chung, D. C., Yu, Z.-F., Tillman, A., Wittes, J., Pappas, J., Elci, O., Marshall, K. A., et al. (2019) · Ophthalmology · doi:10.1016/j.ophtha.2019.06.017 · Cited by 409 · see citing works
Improvement and Decline in Vision with Gene Therapy in Childhood Blindness
Jacobson, S. G., Cideciyan, A. V., Román, A. J., Sumaroka, A., Schwartz, S., Héon, E., & Hauswirth, W. W. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412965 · Cited by 370 · see citing works
AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial
Lv, J., Wang, H., Cheng, X., Chen, Y., Wang, D., Zhang, L., Cao, Q., Tang, H., Hu, S., Gao, K., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(23)02874-x · Cited by 365 · see citing works
Kumaran, N., Moore, A. T., Weleber, R. G., & Michaelides, M. (2017) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2016-309975 · Cited by 334 · see citing works
Self-citationFGF21 gene therapy as treatment for obesity and insulin resistance
Jiménez, V., Jambrina, C., Casana, E., Sacristan, V., MUÑOZ, S. A., Darriba, S., Rodó, J., Mallol, C., García, M., León, X., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201708791 · Cited by 318 · see citing works
Pearson, R. A., Gonzalez-Cordero, A., West, E. L., Ribeiro, J., Aghaizu, N. D., Goh, D., Sampson, R. D., Georgiadis, A., Waldron, P. V., Durán, Y., et al. (2016) · Nature Communications · doi:10.1038/ncomms13029 · Cited by 311 · see citing works
Self-citationAAV <i>cis</i> -regulatory sequences are correlated with ocular toxicity
Xiong, W., Wu, D. M., Xue, Y., Wang, S. K., Chung, M. J., Ji, X., Rana, P., Zhao, S. R., Mai, S., & Cepko, C. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821000116 · Cited by 249 · see citing works
Progress and challenges in viral vector manufacturing
van der Loo, J. C. M., & Wright, J. F. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv451 · Cited by 260 · see citing works
Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps
Duncan, J. L., Pierce, E. A., Laster, A., Daiger, S. P., Birch, D. G., Ash, J. D., Iannaccone, A., Flannery, J. G., Sahel, J., Zack, D. J., et al. (2018) · Translational Vision Science & Technology · doi:10.1167/tvst.7.4.6 · Cited by 250 · see citing works
Bucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242 · see citing works
Ghazi, N. G., Abboud, E. B., Nowilaty, S. R., Alkuraya, H., Alhommadi, A., Cai, H., Hou, R., Deng, W.-T., Boye, S. L., Almaghamsi, A., et al. (2016) · Human Genetics · doi:10.1007/s00439-016-1637-y · Cited by 243 · see citing works
Unraveling the complex story of immune responses to AAV vectors trial after trial.
Vandamme, C., Adjali, O., & Mingozzi, F. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.150 · Cited by 234 · see citing works
Clinical development of gene therapy: results and lessons from recent successes
Kumar, S., Markusic, D., Biswas, M., High, K., & Herzog, R. (2016) · Molecular Therapy: Methods & Clinical Development · doi:10.1038/mtm.2016.34 · Cited by 236 · see citing works
Gene Editing for <i>CEP290</i> -Associated Retinal Degeneration
Pierce, E. A., Aleman, T. S., Jayasundera, K. T., Ashimatey, B. S., Kim, K., Rashid, A., Jaskolka, M. C., Myers, R. L., Lam, B. L., Bailey, S. T., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309915 · Cited by 237 · see citing works
Emerging therapies for inherited retinal degeneration
Scholl, H. P. N., Strauss, R. W., Singh, M. S., Dalkara, D., Roska, B., Picaud, S., & Sahel, J.-A. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2838 · Cited by 219 · see citing works
Pharmaceutical development of AAV-based gene therapy products for the eye
Rodrigues, G. A., Shalaev, E., Karami, T. K., Cunningham, J., Slater, N. K. H., & Rivers, H. M. (2019) · Pharmaceutical Research · doi:10.1007/s11095-018-2554-7 · Cited by 213 · see citing works
Weleber, R. G., Pennesi, M. E., Wilson, D. J., Kaushal, S., Erker, L. R., Jensen, L., McBride, M. T., Flotte, T. R., Humphries, M., Calcedo, R., et al. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.03.003 · Cited by 218 · see citing works
Self-citationEngineering adeno-associated viral vectors to evade innate immune and inflammatory responses
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., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd3438 · Cited by 215 · see citing works
Managing Bardet–Biedl Syndrome—Now and in the Future
Forsythe, E. L., Kenny, J., Bacchelli, C., & Beales, P. L. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00023 · Cited by 214 · see citing works
Luxturna: FDA documents reveal the value of a costly gene therapy
Darrow, J. J. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.01.019 · Cited by 214 · see citing works
Mingozzi, F., & High, K. A. (2017) · Annual Review of Virology · doi:10.1146/annurev-virology-101416-041936 · Cited by 206 · see citing works
Principles of pharmacology in the eye
Awwad, S., Mohamed Ahmed, A. H. A., Sharma, G., Heng, J. S., Khaw, P. T., Brocchini, S., & Lockwood, A. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14024 · Cited by 224 · see citing works
The sound of silence: Transgene silencing in mammalian cell engineering
Cabrera, A., Edelstein, H. I., Glykofrydis, F., Love, K. S., Palacios, S., Tycko, J., Zhang, M., Lensch, S., Shields, C. E., Livingston, M., et al. (2022) · Cell Systems · doi:10.1016/j.cels.2022.11.005 · Cited by 201 · see citing works
Durability of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease
Maguire, A. M., Russell, S., Chung, D. C., Yu, Z.-F., Tillman, A., Drack, A. V., Simonelli, F., Leroy, B. P., Reape, K. Z., High, K. A., et al. (2021) · Ophthalmology · doi:10.1016/j.ophtha.2021.03.031 · Cited by 194 · see citing works
Mechanisms of Photoreceptor Death in Retinitis Pigmentosa
Newton, F. G., & Megaw, R. D. (2020) · Genes · doi:10.3390/genes11101120 · Cited by 200 · see citing works
Visual Acuity after Retinal Gene Therapy for Choroideremia
Edwards, T. L., Jolly, J. K., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Black, G. C., Webster, A. R., Lotery, A. J., Holder, G. E., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1509501 · Cited by 195 · see citing works
Self-citationEarly and late stage gene therapy interventions for inherited retinal degenerations
Botto, C., Rucli, M., Tekinsoy, M. D., Pulman, J., Sahel, J.-A., & Dalkara, D. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100975 · Cited by 190 · see citing works
Technique of retinal gene therapy: delivery of viral vector into the subretinal space
Xue, K., Groppe, M., Salvetti, A. P., & MacLaren, R. E. (2017) · Eye · doi:10.1038/eye.2017.158 · Cited by 191 · see citing works
Biomanufacturing for clinically advanced cell therapies
Aijaz, A., Li, M., Smith, D. W., Khong, D., LeBlon, C. E., Fenton, O. S., Olabisi, R. M., Libutti, S. K., Tischfield, J. A., Maus, M. V., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-018-0246-6 · Cited by 194 · see citing works
Lentiviral Vector Gene Transfer of Endostatin/Angiostatin for Macular Degeneration (GEM) Study
Campochiaro, P. A., Lauer, A. K., Sohn, E. H., Mir, T. A., Naylor, S., Anderton, M. C., Kelleher, M., Harrop, R., Ellis, S., & Mitrophanous, K. A. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.117 · Cited by 186 · see citing works
Gasparini, S. J., Llonch, S., Borsch, O., & Ader, M. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.11.001 · Cited by 185 · see citing works
Clinical Perspective: Treating RPE65-Associated Retinal Dystrophy
Maguire, A. M., Bennett, J., Aleman, E. M., Leroy, B. P., & Alemán, T. S. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.029 · Cited by 183 · see citing works
Jang, H., Jo, D. H., Cho, C. S., Shin, J. H., Seo, J. H., Yu, G., Gopalappa, R., Kim, D., Cho, S., Kim, J. H., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00788-9 · Cited by 184 · see citing works
Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta Experience
Dimopoulos, I. S., Hoang, S. C., Radziwon, A., Binczyk, N. M., Seabra, M. C., MacLaren, R. E., Somani, R., Tennant, M. T. S., & MacDonald, I. M. (2018) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2018.06.011 · Cited by 175 · see citing works
Roska, B., & Sahel, J.-A. (2018) · Nature · doi:10.1038/s41586-018-0076-4 · Cited by 161 · see citing works
Garafalo, A. V., Cideciyan, A. V., Héon, E., Sheplock, R., Pearson, A., WeiYang Yu, C., Sumaroka, A., Aguirre, G. D., & Jacobson, S. G. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100827 · Cited by 173 · see citing works
Inherited retinal diseases: Therapeutics, clinical trials and end points—A review
Georgiou, M., Fujinami, K., & Michaelides, M. (2021) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13917 · Cited by 172 · see citing works
Self-citationSuh, S., Choi, E. H., Leinonen, H., Foik, A. T., Newby, G. A., Yeh, W.-H., Dong, Z., Kiser, P. D., Lyon, D. C., Liu, D. R., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00632-6 · Cited by 162 · see citing works
Gange, W. S., Sisk, R. A., Besirli, C. G., Lee, T. C., Havunjian, M., Schwartz, H., Borchert, M., Sengillo, J. D., Mendoza‐Santiesteban, C. E., Berrocal, A. M., et al. (2021) · Ophthalmology Retina · doi:10.1016/j.oret.2021.03.016 · Cited by 157 · see citing works
AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye
Reichel, F. F., Dauletbekov, D. L., Klein, R., Peters, T., Ochakovski, G. A., Seitz, I. P., Wilhelm, B., Ueffing, M., Biel, M., Wissinger, B., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.08.018 · Cited by 145 · see citing works
Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells
Bassuk, A. G., Zheng, A., Li, Y., Tsang, S. H., & Mahajan, V. B. (2016) · Scientific Reports · doi:10.1038/srep19969 · Cited by 151 · see citing works
Yiu, G., Chung, S. H., Mollhoff, I. N., Nguyen, U. T., Thomasy, S. M., Yoo, J., Taraborelli, D., & Noronha, G. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.01.002 · Cited by 153 · see citing works
Beyond the brain: Optogenetic control in the spinal cord and peripheral nervous system
Montgomery, K. L., Iyer, S. M., Christensen, A. J., Deisseroth, K., & Delp, S. L. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad7577 · Cited by 147 · see citing works
Ju, W., Perkins, G. A., Keun-young Kim, A., Bastola, T., Choi, W.-Y., & Choi, S. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2022.101136 · Cited by 148 · see citing works
Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders
Pavlou, M., Schön, C., Occelli, L. M., Rossi, A., Meumann, N., Boyd, R. F., Bartoe, J. T., Siedlecki, J., Gerhardt, M. J., Babutzka, S., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013392 · Cited by 135 · see citing works
Self-citationLong-term outcomes of gene therapy for the treatment of Leber’s hereditary optic neuropathy
Yang, S., Ma, S.-Q., Wan, X., He, H., Pei, H., Zhao, M.-J., Chen, C., Wang, D.-W., Dong, X.-Y., Yuan, J.-J., et al. (2016) · eBioMedicine · doi:10.1016/j.ebiom.2016.07.002 · Cited by 139 · see citing works
Safety and long-term efficacy of AAV4 gene therapy in patients with RPE65 leber congenital amaurosis
Le Meur, G., Lebranchu, P., Billaud, F., Adjali, O., Schmitt, S., Bézieau, S., Péréon, Y., Valabregue, R., Ivan, C., Darmon, C., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.09.014 · Cited by 137 · see citing works
Gene therapy and genome surgery in the retina
DiCarlo, J. E., Mahajan, V. B., & Tsang, S. H. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120429 · Cited by 127 · see citing works
Gene Therapy 2017: Progress and Future Directions
Keeler, A. M., ElMallah, M. K., & Flotte, T. R. (2017) · Clinical and Translational Science · doi:10.1111/cts.12466 · Cited by 135 · see citing works
Course of Sodium Iodate–Induced Retinal Degeneration in Albino and Pigmented Mice
Chowers, G., Cohen, M. J., Marks-Ohana, D., Stika, S., Eijzenberg, A., Banin, E., & Obolensky, A. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-21255 · Cited by 130 · see citing works
Let There Be Light: Gene and Cell Therapy for Blindness
Dalkara, D., Goureau, O., Marazova, K., & Sahel, J. (2016) · Human Gene Therapy · doi:10.1089/hum.2015.147 · Cited by 129 · see citing works
Gene therapy for <i>RPE65</i>-related retinal disease
Miraldi Utz, V., Coussa, R. G., Antaki, F., & Traboulsi, E. I. (2018) · Ophthalmic Genetics · doi:10.1080/13816810.2018.1533027 · Cited by 126 · see citing works
Current clinical applications of AAV-mediated gene therapy
Byrne, B. J., Flanigan, K. M., Matesanz, S. E., Finkel, R. S., Waldrop, M. A., D'Ambrosio, E. S., Johnson, N. E., Smith, B. K., Bönnemann, C. G., Carrig, S., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.045 · Cited by 134 · see citing works
Seeing the light after 25 Years of retinal gene therapy
Trapani, I., & Auricchio, A. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.06.006 · Cited by 124 · see citing works
AAV-mediated CRISPR/cas gene editing of retinal cells in vivo
Hung, S. S. C., Chrysostomou, V., Li, F., Lim, J. K. H., Wang, J.-H., Powell, J. E., Tu, L., Daniszewski, M., Lo, C., Wong, R. C., et al. (2016) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.16-19316 · Cited by 125 · see citing works
Noninvasive gene delivery to foveal cones for vision restoration
Khabou, H., Garita-Hernandez, M., Chaffiol, A., Reichman, S., Jaillard, C., Brazhnikova, E., Bertin, S., Forster, V., Desrosiers, M., Winckler, C., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.96029 · Cited by 124 · see citing works
Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity
Wang, G., Chow, R. D.-W., Bai, Z., Zhu, L., Errami, Y., Dai, X., Dong, M. B., Ye, L., Zhang, X., Renauer, P. A., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0500-4 · Cited by 121 · see citing works
Review of gene therapies for age-related macular degeneration
Khanani, A. M., Thomas, M. J., Aziz, A. A., Weng, C. Y., Danzig, C. J., Yiu, G., Kiss, S., Waheed, N. K., & Kaiser, P. K. (2022) · Eye · doi:10.1038/s41433-021-01842-1 · Cited by 119 · see citing works
Shao, W., Earley, L. F., Chai, Z., Chen, X., Sun, J., He, T., Deng, M., Hirsch, M. L., Ting, J., Samulski, R. J., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120474 · Cited by 119 · see citing works
In vivo genome editing via the HITI method as a tool for gene therapy
Suzuki, K., & Belmonte, J. C. I. (2017) · Journal of Human Genetics · doi:10.1038/s10038-017-0352-4 · Cited by 115 · see citing works
In vivo–directed evolution of adeno-associated virus in the primate retina
Byrne, L. C., Day, T. P., Visel, M., Strazzeri, J. A., Fortuny, C., Dalkara, D., Merigan, W. H., Schaffer, D. V., & Flannery, J. G. (2020) · JCI Insight · doi:10.1172/jci.insight.135112 · Cited by 104 · see citing works
Tordo, J., O’Leary, C., Antunes, A. S. L. M., Palomar, N., Aldrin-Kirk, P., Basche, M., Bennett, A., D’Souza, Z., Gleitz, H., Godwin, A., et al. (2018) · Brain · doi:10.1093/brain/awy126 · Cited by 113 · see citing works
Self-citationFischer, M. D., McClements, M. E., Martinez-Fernandez de la Camara, C., Bellingrath, J.-S., Dauletbekov, D., Ramsden, S. C., Hickey, D. G., Barnard, A. R., & MacLaren, R. E. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.05.005 · Cited by 112 · see citing works
Taking Stock of Retinal Gene Therapy: Looking Back and Moving Forward
Bennett, J. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.03.008 · Cited by 110 · see citing works
Gene Therapy in Retinal Dystrophies
Ziccardi, L., Cordeddu, V., Gaddini, L., Matteucci, A., Parravano, M., Malchiodi-Albedi, F., & Varano, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225722 · Cited by 107 · see citing works
A look into retinal organoids: methods, analytical techniques, and applications
Afanasyeva, T. A. V., Corral-Serrano, J. C., Garanto, A., Roepman, R., Cheetham, M. E., & Collin, R. W. J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03917-4 · Cited by 101 · see citing works
Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa
Wang, W., Lee, S. J., Scott, P. A., Lu, X., Emery, D., Liu, Y., Ezashi, T., Roberts, M. R., Ross, J. W., Kaplan, H. J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.03.022 · Cited by 105 · see citing works
Sujirakul, T., Lin, M. K., Duong, J., Wei, Y., López‐Pintado, S., & Tsang, S. H. (2015) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2015.06.032 · Cited by 104 · see citing works
Dosage thresholds and influence of transgene cassette in adeno-associated virus–related toxicity
Khabou, H., Cordeau, C., Pacot, L., Fisson, S., & Dalkara, D. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.144 · Cited by 93 · see citing works
Takahashi, K., Igarashi, T., Miyake, K., Kobayashi, M., Yaguchi, C., Iijima, O., Yamazaki, Y., Katakai, Y., Miyake, N., Kameya, S., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2016.10.008 · Cited by 99 · see citing works
“Consistent with that idea, AAV-mediated transduction of the retina in humans, monkeys, and dogs reportedly causes transient inflammation that does not adversely affect visual function.(3,20) In addition, we detected no morphological changes on color fundus images or OCT between the pre-AAV and preeuthanasia injections…”
BackgroundReprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration
Zhang, L., Du, J., Justus, S., Hsu, C., Bonet‐Ponce, L., Wu, W.-H., Tsai, Y.-T., Wu, W., Jia, Y., Duong, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86905 · Cited by 101 · see citing works
Bouquet, C., Vignal Clermont, C., Galy, A., Fitoussi, S., Blouin, L., Munk, M. R., Valero, S., Meunier, S., Katz, B., Sahel, J. A., et al. (2019) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2018.6902 · Cited by 102 · see citing works
Jo, D. H., Song, D. W., Cho, C. S., Kim, U. G., Lee, K. J., Lee, K., Park, S. W., Kim, J., Kim, J. H., Kim, J., et al. (2019) · Science Advances · doi:10.1126/sciadv.aax1210 · Cited by 100 · see citing works
Intravitreal, Subretinal, and Suprachoroidal Injections: Evolution of Microneedles for Drug Delivery
Hartman, R. R., & Kompella, U. B. (2017) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2017.0121 · Cited by 101 · see citing works
Immune Response Mechanisms against AAV Vectors in Animal Models
Martino, A. T., & Markusic, D. M. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.12.008 · Cited by 97 · see citing works
Gene therapy for visual loss: Opportunities and concerns
Lee, J. H., Wang, J.-H., Chen, J., Li, F., Edwards, T. L., Hewitt, A. W., & Liu, G. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.08.003 · Cited by 101 · see citing works
Chiu, W., Lin, T.-Y., Chang, Y.-C., Lai, H. I. A. M., Lin, S.-C., Ma, C., Yarmishyn, A. A., Lin, S.-C., Chang, K.-J., Chou, Y.-B., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094534 · Cited by 98 · see citing works
Choi, E. H., Suh, S., Foik, A. T., Leinonen, H., Newby, G. A., Gao, X. D., Banskota, S., Hoang, T. V., Du, S. W., Dong, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29490-3 · Cited by 97 · see citing works
Leber’s Congenital Amaurosis: Current Concepts of Genotype-Phenotype Correlations
Huang, C.-H., Yang, C., Yang, C., Hou, Y., & Chen, T. (2021) · Genes · doi:10.3390/genes12081261 · Cited by 95 · see citing works
Pharmacological approaches to retinitis pigmentosa: A laboratory perspective
Guadagni, V., Novelli, E., Piano, I., Gargini, C., & Strettoi, E. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.06.005 · Cited by 94 · see citing works
CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES
Talib, M., van Schooneveld, M. J., Thiadens, A. A. H. J., Fiocco, M. F., Wijnholds, J., Florijn, R. J., Schalij-Delfos, N. E., van Genderen, M. M., Putter, H., Cremers, F. P. M., et al. (2018) · Retina · doi:10.1097/iae.0000000000002125 · Cited by 92 · see citing works
de Guimarães, T. A. C., Georgiou, M., Bainbridge, J. W., & Michaelides, M. (2020) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2020-316195 · Cited by 92 · see citing works
Self-citationBeltran, W. A., Cideciyan, A. V., Iwabe, S., Świder, M., Kosyk, M. S., McDaid, K. S., Martynyuk, I., Ying, G., Shaffer, J., Deng, W., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509914112 · Cited by 90 · see citing works
Retinitis pigmentosa: recent advances and future directions in diagnosis and management
Fahim, A. T. (2018) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000000690 · Cited by 90 · see citing works
Gene therapy for inherited retinal and optic nerve degenerations
Moore, N. A., Morral, N., Ciulla, T. A., & Bracha, P. (2017) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1389886 · Cited by 89 · see citing works
Newman, N. J., Yu-Wai-Man, P., Subramanian, P. S., Moster, M. L., Wang, A.-G., Donahue, S. P., Leroy, B. P., Carelli, V., Biousse, V., Vignal-Clermont, C., et al. (2023) · Brain · doi:10.1093/brain/awac421 · Cited by 87 · see citing works
Georgiadis, A., Duran, Y., Ribeiro, J., Abelleira-Hervas, L., Robbie, S. J., Sünkel-Laing, B., Fourali, S., Gonzalez-Cordero, A., Cristante, E., Michaelides, M., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.66 · Cited by 84 · see citing works
Self-citation
- Authors
- Bainbridge, J. W. B., Mehat, M. S., Sundaram, V., Robbie, S. J., Barker, S. E., Ripamonti, C., Georgiadis, A., Mowat, F. M., Beattie, S. G., Gardner, P. J., Feathers, K. L., Luong, V. A., Yzer, S., Balaggan, K., Viswanathan, A., de Ravel, T. J. L., Casteels, I., Holder, G. E., Tyler, N., Fitzke, F. W., Weleber, R. G., Nardini, M., Moore, A. T., Thompson, D. A., Petersen-Jones, S. M., Michaelides, M., van den Born, L. I., Stockman, A., Smith, A. J., Rubin, G., & Ali, R. R.
- Affiliations
- Moorfields Eye Hospital (GB)
- Michigan State University (US)
- University of Michigan (US)
- Rotterdam Eye Hospital (NL)
- Universitair Ziekenhuis Leuven (BE)
- Oregon Health & Science University (US)
- ORCID
- Bainbridge, James W.B.
- Sundaram, Venki
- Robbie, Scott J.
- Georgiadis, Anastasios
- Mowat, Freya M.
- Beattie, Stuart G.
- Yzer, Suzanne
- Balaggan, Kamaljit
- Viswanathan, Ananth
- Casteels, Ingele
- Holder, Graham E.
- Tyler, Nick
- Weleber, Richard G.
- Moore, Anthony T.
- Thompson, Debra A.
- Michaelides, Michel
- Smith, Alexander J.
- Rubin, Gary
- Ali, Robin R.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-05-14
- Volume
- 372
- Issue
- 20
- Pages
- 1887-1897
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4497809
- OpenAlex
- W265142245
- Semantic Scholar
- 31832b3aa3500171fc5f2a951f0a4124bd40068d
- Cited by
- 743
- References
- 29
- Citations by year
- 2026: 36 · 2025: 36 · 2024: 46 · 2023: 44 · 2022: 63 · 2021: 92 · 2020: 81 · 2019: 68 · 2018: 79 · 2017: 97 · 2016: 72 · 2015: 27 · 2014: 1
- FWCI
- 39.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Durham Research Online (Durham University) (acceptedVersion)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Research to Prevent Blindness
- Wellcome Trust
- Massachusetts Medical Society
- National Institute for Health and Care Research (NF-SI-0507-10204, NF-SI-0513-10074, NIHR-RP-011-003)
- Sir Jules Thorn Charitable Trust
- University College London
- European Commission
- Ulverscroft Foundation
- Durham University
- KU Leuven
- Moorfields Eye Hospital NHS Foundation Trust
- Directorate for Biological Sciences
- Medical Research Council (MR/K024000/1, MR/M015815/1, MR/J005215/1)
- Engineering and Physical Sciences Research Council (EP/J017698/1, EP/J005193/1)
- Biotechnology and Biological Sciences Research Council (BB/M00211X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- Leber congenital amaurosis, RPE65, gene therapy, retinal degeneration, visual function, retinal sensitivity, electroretinogram, vector dose, intraocular inflammation, visual acuity, canine model, species differences, long-term efficacy and safety
- MeSH terms
- Retinoid Isomerohydrolase, Dependovirus, Adolescent, Animals, Child, Disease Models, Animal, Dogs, Genetic Vectors, Humans, Mutation, Retina, Vision, Ocular, Genetic Therapy, DNA, Complementary, Disease Progression, cis-trans-Isomerases, Photoreceptor Cells, Vertebrate, Young Adult, Leber Congenital Amaurosis
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.
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
