Recombinant Adeno-Associated Viral Vectors Mediate Long-Term Transgene Expression in Muscle
Abstract
Gene transfer to muscle holds overt promise for the treatment of inherited myopathies, lysosomal storage disorders, and serum protein deficiencies. In addition, muscle could provide a reservoir for delivery of therapeutic molecules like blood clotting factors, erythropoietin, or insulin. To date, successful gene transfer to muscle has been limited by the inefficiency of the vector delivery systems and the transient nature of gene expression. In this paper, we show that a vector based on recombinant adeno-associated virus (rAAV) can efficiently transduce adult mouse skeletal muscle. Transduced myofibers escape immune elimination and transgene expression is robust beyond 5 months. Importantly, input vector DNA appears to undergo conversion from single-stranded genomes to high-molecular-weight concatameric forms. These data suggest that rAAV might have a significant advantage over many other viral and nonviral gene delivery methods, and holds significant promise as a vector for gene transfer to mature muscle.
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AAV vectors with two complementary ITRs can form circular concatamers.
“AAV vectors with two complementary ITRs can form circular concatamers. 13-16”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [13]
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- Authors
- Clark, K. R., Sferra, T. J., & Johnson, P. R.
- Affiliations
- Nationwide Children's Hospital (US)
- Corresponding author
- Johnson, Philip R.
- ORCID
- Sferra, Thomas J.
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 1997-04-10
- Volume
- 8
- Issue
- 6
- Pages
- 659-669
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W1979746830
- Cited by
- 153
- References
- 62
- Citations by year
- 2026: 1 · 2024: 1 · 2020: 3 · 2019: 3 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 4
- FWCI
- 14.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Gene Therapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- recombinant adeno-associated virus, skeletal muscle transduction, long-term transgene expression, concatemeric DNA, immune evasion, neutralizing antibodies, vector immunogenicity, inherited myopathies, lysosomal storage disease
- MeSH terms
- Dependovirus, Animals, beta-Galactosidase, DNA, Recombinant, Gene Expression Regulation, HeLa Cells, Humans, Mice, Inbred BALB C, Gene Transfer Techniques, Muscle, Skeletal, Transgenes, Mice
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