Immediate and Long-Term Safety of Recombinant Adeno-associated Virus Injection into the Nonhuman Primate Muscle
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Previous studies on distribution and toxicity of viral vectors administered in monkeys indicated that the nonhuman primate model has a reasonable predictive value for clinical applications. In this study, eight macaques were injected intramuscularly with recombinant adeno-associated virus (rAAV) at doses similar to those administered to hemophilia B patients, and followed to analyze the dissemination and shedding in biological samples and long-term persistence in distant organs. Following rAAV delivery, we found vector genome in various biological fluids for up to 6 days and infectious particles exclusively in the serum during the first 48-72 hours. rAAV sequences were detected in peripheral blood mononuclear cells (PBMC) for up to 10 months. At necropsy, 8 to 18 months after rAAV delivery, rAAV sequences were found in lymph nodes and livers but never in the gonads. Tissue examination, of liver in particular, showed no abnormalities. We concluded that during our experimental time frame, rAAV-mediated gene transfer into skeletal muscle of macaques seemed to be safe with respect to the recipient and the environment. However, it was associated with a transient viremia and the persistence of rAAV sequences in PBMC, lymph nodes, and liver, the long-term consequences of which remain unknown.
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Some vectors used in gene therapy research can be excreted from the body for at least a week after injection.
“There have been studies that have shown that some of the vectors used in gene therapy research can be excreted from the body for a least a week after injection.32”
From Viral Vector Systems for Gene Therapy: A Comprehensive Literature Review of Progress and Biosafety Challenges (2020) · cites this paper as [32]
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- Authors
- Favre, D., Provost, N., Blouin, V., Blancho, G., Chérel, Y., Salvetti, A., & Moullier, P.
- Affiliations
- Inserm (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Corresponding author
- Moullier, Philippe
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 4
- Issue
- 6
- Pages
- 559-566
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W1998214570
- Cited by
- 122
- References
- 34
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 3
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- 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 › Hematology › Hemophilia Treatment and Research
- Keywords
- recombinant adeno-associated virus, nonhuman primate model, macaque, intramuscular injection, viremia, peripheral blood mononuclear cells, lymph nodes, liver, long-term persistence
- MeSH terms
- Dependovirus, Animals, Defective Viruses, DNA, Viral, Female, Injections, Intramuscular, Liver, Lymph Nodes, Macaca fascicularis, Male, Safety, Virion, Polymerase Chain Reaction, Genome, Viral, Virus Shedding, DNA Primers, Muscle, Skeletal
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