ArticleGene therapy2016
Development of an optimized AAV2/5 gene therapy vector for Leber congenital amaurosis owing to defects in RPE65.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 3 of them syntheses that pooled it.
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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
43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Changing trends in the development of AAV-based gene therapies: a meta-analysis of past and present therapies.Gene therapy · 2023Pooled it
- Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.Frontiers in medicine · 2021Pooled it
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Results at 5 Years After Gene Therapy for RPE65-Deficient Retinal Dystrophy.Human gene therapy · 2018Trial
- Personalized Pathogenicity Assessment ofInternational journal of molecular sciences · 2026Article
- A Comprehensive Review of Clinically Applied Adeno-Associated Virus-Based Gene Therapies for Ocular Disease.Human gene therapy · 2025Review
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Evaluating the feasibility of gene replacement strategies to treat MTRFR deficiency.Disease models & mechanisms · 2025Article
- Advances in technical methods and applications of subretinal injections in experimental animals.Frontiers in veterinary science · 2025Review
- Therapeutic landscape of Fabry disease: advances and challenges from classical strategies to emerging therapies.Frontiers in medicine · 2025Review
- Review
- Overview of Retinal Gene Therapy: Current Status and Future Challenges.Cold Spring Harbor perspectives in medicine · 2023Review
- Gene Supplementation in Mice Heterozygous for the D477G RPE65 Variant Implicated in Autosomal Dominant Retinitis Pigmentosa.Human gene therapy · 2023Article
- Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters.Gene therapy · 2023Article
- Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model.Current medical science · 2023Article
- Magnetofection of miR-21 promoted by electromagnetic field and iron oxide nanoparticles via the p38 MAPK pathway contributes to osteogenesis and angiogenesis for intervertebral fusion.Journal of nanobiotechnology · 2023Article
- Intravitreal Injection of AAV for the Transduction of Mouse Retinal Ganglion Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- AAV2-mediated gene therapy for Bietti crystalline dystrophy provides functional CYP4V2 in multiple relevant cell models.Scientific reports · 2022Article
- mTORC1 regulates high levels of protein synthesis in retinal ganglion cells of adult mice.The Journal of biological chemistry · 2022Article
- Subretinal injection in mice to study retinal physiology and disease.Nature protocols · 2022Review
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Leber congenital amaurosis is a group of inherited retinal dystrophies that cause severe sight impairment in childhood; RPE65-deficiency causes impaired rod photoreceptor function from birth and progressive impairment of cone photoreceptor function associated with retinal degeneration. In animal models of RPE65 deficiency, subretinal injection of recombinant adeno-associated virus (AAV) 2/2 vectors carrying RPE65 cDNA improves rod photoreceptor function, and intervention at an early stage of disease provides sustained benefit by protecting cone photoreceptors against retinal degeneration. In affected humans, administration of these vectors has resulted to date in relatively modest improvements in photoreceptor function, even when retinal degeneration is comparatively mild, and the duration of benefit is limited by progressive retinal degeneration. We conclude that the demand for RPE65 in humans is not fully met by current vectors, and predict that a more powerful vector will provide more durable benefit. With this aim we have modified the original AAV2/2 vector to generate AAV2/5-OPTIRPE65. The new configuration consists of an AAV vector serotype 5 carrying an optimized hRPE65 promoter and a codon-optimized hRPE65 gene. In mice, AAV2/5-OPTIRPE65 is at least 300-fold more potent than our original AAV2/2 vector.
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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 OpenQuestion graph.