ArticleScience advances2025
Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- [Genetic therapies for Stargardt disease].Die Ophthalmologie · 2026Review
- A protein chaperone can stabilize the intein-containing precursor to indirectly promote protein splicing.Protein science : a publication of the Protein Society · 2026Article
- Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.Stem cells (Dayton, Ohio) · 2026Article
- Overcoming size barriers in retinal gene therapy via lipid nanoparticle-mediated delivery of full-length eys DNA.Drug delivery and translational research · 2026Article
- Update on the Management of ABCA4 Retinopathy (Stargardt Disease).Ophthalmology and therapy · 2026Review
- Modalities of vision restoration in optic neuropathies and retinal disease.Progress in retinal and eye research · 2026Review
- AAV-based gene therapies for neovascular AMD.Gene therapy · 2026Review
- Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study.BMC medicine · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Subretinal Injection Volume Correlates to Persistent Outer Retinal Thinning in the Pig Eye.Investigative ophthalmology & visual science · 2025Article
- Validation of a Göttingen Minipig Gene Therapy Biodistribution Assay for AVGN7 Using Droplet Digital Polymerase Chain Reaction.The AAPS journal · 2025Article
- RP1 Dual-AAV Gene Therapy Preserves Retinal Structure and Ameliorates Photoreceptor Degeneration in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinal gene therapy using dual adeno-associated viral (AAV) intein vectors can be applied to genetic forms of blindness caused by mutations in genes with coding sequences that exceed single AAV cargo capacity, such as Stargardt disease (STGD1), the most common inherited macular dystrophy. In view of clinical translation of dual AAV intein vectors, here we set to evaluate both the efficiency and safety of their subretinal administration in relevant large animal models. Accordingly, we have developed the first pig model of STGD1, which we found to accumulate lipofuscin similarly to patients. This accumulation is significantly reduced upon subretinal administration of dual AAV intein vectors whose safety and pharmacodynamics we then tested in nonhuman primates, which showed modest and reversible inflammation as well as high levels of photoreceptor transduction. This bodes well for further clinical translation of dual AAV intein vectors in patients with STGD1 as well as for other blinding diseases that require the delivery of large genes.
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