A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs
Open accessAbstract
The success of many gene therapy applications hinges on efficient whole body transduction. In the case of muscular dystrophies, a therapeutic vector has to reach every muscle in the body. Recent studies suggest that vectors based on adeno-associated virus (AAV) are capable of body-wide transduction in rodents. However, translating this finding to large animals remains a challenge. Here we explored systemic gene delivery with AAV serotype-9 (AAV-9) in neonatal dogs. Previous attempts to directly deliver AAV to adult canine muscle have yielded minimal transduction due to a strong cellular immune response. However, in neonatal dogs we observed robust skeletal muscle transduction throughout the body after a single intravenous injection. Importantly, systemic transduction was achieved in the absence of pharmacological intervention or immune suppression and it lasted for at least 6 months (the duration of study). We also observed several unique features not predicted by murine studies. In particular, cardiac muscle was barely transduced in dogs. Many muscular dystrophy patients can be identified by neonatal screening. The technology described here may lead to an effective early intervention in these patients.
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Intravenous delivery of AAV-9 failed to transduce cardiomyocytes in dogs.
“in one study intravenous delivery of AAV-9 failed to transduce cardiomyocytes in dogs”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Yue, et al., 2008
In one study by Yue et al., jugular vein injection of AAV-9 in neonatal dogs successfully transduced skeletal tissue but failed to transduce cardiac muscle.
“In one study by Yue et al. jugular vein injected AAV-9 in neonatal dogs while successfully transduced skeletal tissue, it failed to do so with cardiac muscle (Yue, et al., 2008).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Yue, et al., 2008
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Self-citation
- Authors
- Yue, Y., Ghosh, A., Long, C., Bostick, B., Smith, B. F., Kornegay, J. N., & Duan, D.
- Affiliations
- University of Missouri (US)
- Auburn University (US)
- Corresponding author
- Duan, Dongsheng
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 16
- Issue
- 12
- Pages
- 1944-1952
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC2703820
- OpenAlex
- W2001979917
- Cited by
- 173
- References
- 41
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 12 · 2018: 7 · 2017: 10 · 2016: 7 · 2015: 15 · 2014: 9 · 2013: 12 · 2012: 12
- FWCI
- 10.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R21NS062934, NS-62934)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR057209, AR49419, AR 57209, R01AR049419)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- AAV9, skeletal muscle, systemic gene delivery, intravenous injection, neonatal dogs, muscular dystrophy, early intervention, cell-mediated immunity, large animal model
- MeSH terms
- Dependovirus, Animals, Animals, Newborn, Dogs, Genetic Vectors, Injections, Intravenous, Microcirculation, Muscle, Skeletal, Transgenes
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