Cited by 122Virus-based gene therapy researchRNA Interference and Gene DeliveryHemophilia Treatment and Research

Immediate and Long-Term Safety of Recombinant Adeno-associated Virus Injection into the Nonhuman Primate Muscle

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Favre, David, Provost, Nathalie, Blouin, Véronique, Blancho, Gilles, Chérel, Yan, Salvetti, Anna, Moullier, Philippe·2001·Molecular Therapy

Abstract

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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Registry

Crossref · 10.1006/mthe.2001.0494

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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
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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