ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 218 citations in OpenAlex.
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.Human gene therapy · 2011Trial
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- Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Current Progress and Future Outlook for Synthetic Gene Circuits in Cardiovascular Therapy.Biomolecules · 2026Review
- Emerging Role and Potential Therapeutic Application of TRIM Proteins in Cardiovascular Diseases.Biomolecules · 2026Review
- High-throughput evaluation of cardiac-specific promoters for adeno-associated virus mediated cardiac gene therapy.Gene therapy · 2026Article
- Article
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Directed evolution of liver-detargeted AAV vectors for systemic gene delivery to skeletal muscle and heart.Molecular therapy. Methods & clinical development · 2025Article
- Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025Review
- AAV6 vectors provide superior gene transfer compared to AAV9 vectors following intramyocardial administration.Molecular therapy. Methods & clinical development · 2025Article
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- Engineering Targeted Gene Delivery Systems for Primary Hereditary Skeletal Myopathies: Current Strategies and Future Perspectives.Biomedicines · 2025Review
- Optimized genomic editing of a common Duchenne muscular dystrophy mutation in patient-derived muscle cells and a new humanized mouse model.Molecular therapy. Nucleic acids · 2025Article
- Clinically translatable mitochondrial gene therapy in muscle using tandem mtZFN architecture.EMBO molecular medicine · 2025Article
- A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome.Developmental neuroscience · 2025Review
80 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We report the generation of a new class of adeno-associated virus serotype 9 (AAV9)-derived vectors displaying selective loss of liver tropism and demonstrating potential for cardiac and musculoskeletal gene transfer applications. Random mutagenesis of residues within a surface-exposed region of the major AAV9 capsid protein yielded a capsid library with mutations clustered at the icosahedral threefold symmetry axis. Using a combination of sequence analysis, structural models, and in vivo screening, we identified several functionally diverse AAV9 variants. The latter were classified into three functional subgroups, with respect to parental AAV9 displaying: (i) decreased transduction efficiency across multiple tissues; (ii) a selective decrease in liver transduction, or (iii) a similar transduction profile. Notably, variants 9.45 and 9.61 (subgroup II) displayed 10- to 25-fold lower gene transfer efficiency in liver, while transducing cardiac and skeletal muscle as efficiently as AAV9. These results were further corroborated by quantitation of vector genome copies and histological analysis of reporter (tdTomato) gene expression. The study highlights the feasibility of generating AAV vectors with selectively ablated tissue tropism, which when combined with other targeting strategies could allow sharply segregated gene expression. Liver-detargeted AAV9 variants described herein are excellent candidates for preclinical evaluation in animal models of cardiac and musculoskeletal disease.
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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.