ArticleScience translational medicine2019
Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 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.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Optogenetic vision restoration: translational barriers and emerging therapeutic strategies.Gene therapy · 2026Review
- Article
- Loss of ABCA4 from photoreceptor discs is associated with glial transcriptomic changes in retinal organoids.Stem cells (Dayton, Ohio) · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Organoids - the future of pre-clinical development of AAV gene therapy for CNS disorders.Gene therapy · 2026Review
- Advances in neural organoids: structural organization, disease modeling, and applications in gene therapy.Molecular biology reports · 2026Review
- Long-term restoration of auditory function in a DFNA2 mouse model by adenine base editing.EMBO molecular medicine · 2026Article
- Non-clinical safety considerations on genome editing using the CRISPR/Cas system.Genes & diseases · 2026Review
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Disease exacerbation in human DMD MYOrganoids enables gene therapy evaluation and unveils persistence of fibrotic activity.NPJ Regenerative medicine · 2026Article
- 3D Quantification of Viral Transduction Efficiency in Living Human Retinal Organoids.Small methods · 2026Article
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Efficient kidney gene transfer and proximal tubule transduction using self-complementary AAV.cc47 vectors.Molecular therapy. Methods & clinical development · 2025Article
- Genetic mutations in HSV-1 replication-defective vectors: Implications for their safety in gene therapy applications.Gene therapy · 2025Article
- Base and Prime Editing for Inherited Retinal Diseases: Delivery Platforms, Safety, Efficacy, and Translational Perspectives.Pharmaceutics · 2025Review
- Engineering adeno-associated viral vectors for CRISPR/Cas based in vivo therapeutic genome editing.Biomaterials · 2025Review
- One down but many more to go: the state of gene therapy for inherited retinal disease.Regenerative medicine · 2025Review
- RP1 Dual-AAV Gene Therapy Preserves Retinal Structure and Ameliorates Photoreceptor Degeneration in a Murine Model of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Generation and evaluation of a novel PI3K-targeting gene therapy in the failing mouse heart and healthy sheep heart.Journal of molecular and cellular cardiology plus · 2025Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
Retinal gene therapy with adeno-associated viral (AAV) vectors holds promises for treating inherited and noninherited diseases of the eye. Although clinical data suggest that retinal gene therapy is safe and effective, delivery of large genes is hindered by the limited AAV cargo capacity. Protein trans-splicing mediated by split inteins is used by single-cell organisms to reconstitute proteins. Here, we show that delivery of multiple AAV vectors each encoding one of the fragments of target proteins flanked by short split inteins results in protein trans-splicing and full-length protein reconstitution in the retina of mice and pigs and in human retinal organoids. The reconstitution of large therapeutic proteins using this approach improved the phenotype of two mouse models of inherited retinal diseases. Our data support the use of split intein-mediated protein trans-splicing in combination with AAV subretinal delivery for gene therapy of inherited blindness due to mutations in large genes.
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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.