ArticleHuman gene therapy. Clinical development2017
Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3-Mutant Dogs.
Article in Human gene therapy. Clinical development, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- Novel photoreceptor-specific promoters for gene therapy in mid- to late-stage retinal degeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Canine models of inherited retinal diseases: from neglect to well-recognized translational value.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Ocular Gene Therapy: An Overview of Viral Vectors, Immune Responses, and Future Directions.The Yale journal of biology and medicine · 2024Review
- Pig Models in Retinal Research and Retinal Disease.Cold Spring Harbor perspectives in medicine · 2024Review
- Seeing the Future: A Review of Ocular Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- Canine and Feline Models of Inherited Retinal Diseases.Cold Spring Harbor perspectives in medicine · 2024Review
- Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.Biomedicines · 2023Review
- Outer retinal transduction by AAV2-7m8 following intravitreal injection in a sheep model of CNGA3 achromatopsia.Gene therapy · 2022Article
- Targeting ON-bipolar cells by AAV gene therapy stably reversesProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Achromatopsia: Genetics and Gene Therapy.Molecular diagnosis & therapy · 2022Review
- Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy.International journal of molecular sciences · 2021Review
- Ocular Inflammation and Treatment Emergent Adverse Events in Retinal Gene Therapy.International ophthalmology clinics · 2021Article
- Delivering AAV to the Central Nervous and Sensory Systems.Trends in pharmacological sciences · 2021Review
- Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives.Progress in retinal and eye research · 2020Review
- Review
- Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.Molecular therapy. Methods & clinical development · 2020Article
- AAV-mediated human CNGB3 restores cone function in an all-cone mouse model ofJournal of biomedical research · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Achromatopsia is an inherited retinal disorder of cone photoreceptors characterized by markedly reduced visual acuity, extreme light sensitivity, and absence of color discrimination. Approximately 50% of cases are caused by mutations in the cone photoreceptor-specific cyclic nucleotide gated channel beta subunit (CNGB3) gene. Studies in CNGB3-mutant dogs showed that subretinal injection of an AAV vector expressing human CNGB3, which has 76% amino acid identity with canine CNGB3, driven by a 2.1 kb human red cone opsin promoter (PR2.1) and packaged in AAV5 capsids (AAV5-PR2.1-hCNGB3) rescued cone photoreceptor function, but at high doses was associated with an inflammatory response (focal chorioretinitis) consistent with immune-mediated toxicity. AAV vectors containing the PR2.1 promoter packaged in AAV5 capsids and expressing either the native canine CNGB3 (AAV5-PR2.1-cCNGB3) or the human CNGB3 (AAV5-PR2.1-hCNGB3) were evaluated at different dose levels in CNGB3-mutant dogs. The vector expressing canine CNGB3 achieved somewhat better rescue of cone function but unexpectedly was associated with a greater degree of retinal toxicity than the vector expressing human CNGB3. Very low-level T-cell immune responses to some AAV or CNGB3 peptides were observed in animals that received the higher vector dose. There was a more than twofold increase in serum neutralizing antibodies to AAV in one of three animals in the low-dose group and in two of three animals in the high-dose group. No serum anti-hCNGB3 antibodies were detected in any animal. The results of this study do not support the hypothesis that the focal chorioretinitis seen with high doses of AAV5-PR2.1-hCNGB3 in the initial studies was due to an immune response to human CNGB3.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.