ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Intravitreal injection of a rationally designed AAV capsid library in non-human primate identifies variants with enhanced retinal transduction and neutralizing antibody evasion.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- AAV Gene Therapy Drug Development and Translation of Engineered Ocular and Neurotropic Capsids: A Systematic Review Using Natural Language Processing.Clinical and translational science · 2025Pooled it
- Hierarchical ROS-scavenging hydrogel system for coordinating the modulation of RGC necroptosis and oxidative stress in an acute glaucoma model.Bioactive materials · 2026Article
- Deep-sequencing-guided library screening and profiling of AAV capsids in the primate retina.Molecular therapy. Advances · 2026Article
- Laterally spreading AAV.SPR enables safe and efficient RS1 delivery to the macula after peripheral subretinal injection.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- The internal limiting basement membrane inhibits functional engraftment of transplanted human retinal ganglion cells in vivo.Science translational medicine · 2026Article
- Capsid-engineered AAV vector overcomes a key intracellular barrier and efficiently transduces spiral ganglion neurons in adult mice.Molecular therapy. Advances · 2026Article
- AAV2-Retro-Mediated Gene Transfer Selectively Targets Outer Retinal Cells Following Intravitreal Injection.Investigative ophthalmology & visual science · 2026Article
- Development of an AAV-based gene therapy for the ocular phenotype of Friedreich's ataxia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Base and Prime Editing for Inherited Retinal Diseases: Delivery Platforms, Safety, Efficacy, and Translational Perspectives.Pharmaceutics · 2025Review
- A Comprehensive Review of Clinically Applied Adeno-Associated Virus-Based Gene Therapies for Ocular Disease.Human gene therapy · 2025Review
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- Strategies of AAV capsid engineering for targeted delivery to brain, muscle, and retina.Frontiers in molecular biosciences · 2025Review
- Intravitreal AAV2 gene delivery to feline retinal ganglion cells.Vision research · 2025Article
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Bypassing pre-existing antibodies extends the applicability of AAV-based retinal therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) continues to be the gold standard vector for therapeutic gene delivery and has proven especially useful for treating ocular disease. Intravitreal injection (IVtI) is a promising delivery route because it increases accessibility of gene therapies to larger patient populations. However, data from clinical and non-human primate (NHP) studies utilizing currently available capsids indicate that anatomical barriers to AAV and pre-existing neutralizing antibodies can restrict gene expression to levels that are "sub-therapeutic" in a substantial proportion of patients. Here, we performed a combination of directed evolution in NHPs of an AAV2-based capsid library with simultaneous mutations across six surface-exposed variable regions and rational design to identify novel capsid variants with improved retinal transduction following IVtI. Following two rounds of screening in NHP, enriched variants were characterized in intravitreally injected mice and NHPs and shown to have increased transduction relative to AAV2. Lead capsid variant, P2-V1, demonstrated an increased ability to evade neutralizing antibodies in human vitreous samples relative to AAV2 and AAV2.7m8. Taken together, this study further contributed to our understanding of the selective pressures associated with retinal transduction via the vitreous and identified promising novel AAV capsid variants for clinical consideration.
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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.