ArticleHuman molecular genetics2015
Improved dual AAV vectors with reduced expression of truncated proteins are safe and effective in the retina of a mouse model of Stargardt disease.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- 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
- Incorporating AI-optimized zinc finger proteins enhances the efficiencies and targeting ranges of miniature base editors.Nature communications · 2026Article
- Update on the Management of ABCA4 Retinopathy (Stargardt Disease).Ophthalmology and therapy · 2026Review
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 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
- Dual AAV vectors for efficient delivery of large transgenes.Nature protocols · 2026Review
- Efficient kidney gene transfer and proximal tubule transduction using self-complementary AAV.cc47 vectors.Molecular therapy. Methods & clinical development · 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
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Gene therapy shines light on congenital stationary night blindness for future cures.Journal of translational medicine · 2025Review
- Retinal gene therapy for Stargardt disease with dual AAV intein vectors is both safe and effective in large animal models.Science advances · 2025Article
- Genetic engineering and the eye.Eye (London, England) · 2025Review
- Delivering large genes using adeno-associated virus and the CRE-lox DNA recombination system.Human molecular genetics · 2024Article
- Translatability barriers between preclinical and clinical trials of AAV gene therapy in inherited retinal diseases.Vision research · 2023Review
- Assessment of Therapeutic Potential of a Dual AAV Approach for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2023Article
- Extending AAV Packaging Cargo through Dual Co-Transduction: Efficient Protein Trans-Splicing at Low Vector Doses.International journal of molecular sciences · 2023Article
- Bioengineering strategies for restoring vision.Nature biomedical engineering · 2023Review
- Development of a dual hybrid AAV vector for endothelial-targeted expression of von Willebrand factor.Gene therapy · 2023Article
- Developing New Vectors for Retinal Gene Therapy.Cold Spring Harbor perspectives in medicine · 2023Article
- Identifying and Overcoming Challenges in Developing Effective Treatments for Usher 1B: A Workshop Report.Translational vision science & technology · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Stargardt disease (STGD1) due to mutations in the large ABCA4 gene is the most common inherited macular degeneration in humans. We have shown that dual adeno-associated viral (AAV) vectors effectively transfer ABCA4 to the retina of Abca4-/- mice. However, they express both lower levels of transgene compared with a single AAV and truncated proteins. To increase productive dual AAV concatemerization, which would overcome these limitations, we have explored the use of either various regions of homology or heterologous inverted terminal repeats (ITR). In addition, we tested the ability of various degradation signals to decrease the expression of truncated proteins. We found the highest levels of transgene expression using regions of homology based on either alkaline phosphatase or the F1 phage (AK). The use of heterologous ITR does not decrease the levels of truncated proteins relative to full-length ABCA4 and impairs AAV vector production. Conversely, the inclusion of the CL1 degradation signal results in the selective degradation of truncated proteins from the 5'-half without affecting full-length protein production. Therefore, we developed dual AAV hybrid ABCA4 vectors including homologous ITR2, the photoreceptor-specific G protein-coupled receptor kinase 1 promoter, the AK region of homology and the CL1 degradation signal. We show that upon subretinal administration these vectors are both safe in pigs and effective in Abca4-/- mice. Our data support the use of improved dual AAV vectors for gene therapy of STGD1.
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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.