ArticleMolecular therapy. Methods & clinical development2015
A comparison of AAV strategies distinguishes overlapping vectors for efficient systemic delivery of the 6.2 kb Dysferlin coding sequence.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- FAP adipogenesis drives early spinal muscle loss in dysferlinopathy and reveals a therapeutic target.EMBO molecular medicine · 2026Article
- 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
- SauCas9-based cell cycle-dependent genome editing via AAV delivery.Molecular therapy. Advances · 2026Article
- DAB2 in LGMD R2: a molecular link between disease progression and lipid dysregulation.JCI insight · 2026Article
- Dysferlin and the Regulation of CaCells · 2025Review
- Evaluation of the loading capacity and patterns of packaged DNA in AAV genomes of different sizes using long-read sequencing.Molecular therapy. Methods & clinical development · 2025Article
- Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.Nature communications · 2024Article
- Nanodysferlins support membrane repair and binding to TRIM72/MG53 but do not localize to t-tubules or stabilize CaMolecular therapy. Methods & clinical development · 2024Article
- Limb Girdle Muscular Dystrophy Type 2B (LGMD2B): Diagnosis and Therapeutic Possibilities.International journal of molecular sciences · 2024Review
- Optimization strategies and advances in the research and development of AAV-based gene therapy to deliver large transgenes.Clinical and translational medicine · 2024Review
- The Dysferlinopathies Conundrum: Clinical Spectra, Disease Mechanism and Genetic Approaches for Treatments.Biomolecules · 2024Review
- Portrait of Dysferlinopathy: Diagnosis and Development of Therapy.Journal of clinical medicine · 2023Review
- Dual Adeno-Associated Virus 9 with Codon-Optimized DYSF Gene Promotes In Vivo Muscle Regeneration and May Decrease Inflammatory Response in Limb Girdle Muscular Dystrophy Type R2.International journal of molecular sciences · 2023Article
- Assessment of Therapeutic Potential of a Dual AAV Approach for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2023Article
- Review
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Secreted acid sphingomyelinase as a potential gene therapy for limb girdle muscular dystrophy 2B.The Journal of clinical investigation · 2022Article
- Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss.Molecular therapy. Methods & clinical development · 2021Review
- Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid.Pharmaceutics · 2020Review
- Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness.Frontiers in molecular neuroscience · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adeno-associated virus (rAAV) is currently the best vector for gene delivery into the skeletal muscle. However, the 5-kb packaging size of this virus is a major obstacle for large gene transfer. This past decade, many different strategies were developed to circumvent this issue (concatemerization-splicing, overlapping vectors, hybrid dual or fragmented AAV). Loss of function mutations in the DYSF gene whose coding sequence is 6.2kb lead to progressive muscular dystrophies (LGMD2B: OMIM_253601; MM: OMIM_254130; DMAT: OMIM_606768). In this study, we compared large gene transfer techniques to deliver the DYSF gene into the skeletal muscle. After rAAV8s intramuscular injection into dysferlin deficient mice, we showed that the overlap strategy is the most effective approach to reconstitute a full-length messenger. After systemic administration, the level of dysferlin obtained on different muscles corresponded to 0.5- to 2-fold compared to the normal level. We further demonstrated that the overlapping vector set was efficient to correct the histopathology, resistance to eccentric contractions and whole body force in the dysferlin deficient mice. Altogether, these data indicate that using overlapping vectors could be a promising approach for a potential clinical treatment of dysferlinopathies.
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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.