Intramuscular injection of rAAV in macaques appeared safe with no tissue abnormalities at 8 to 18 months, despite transient viremia and persistence of rAAV sequences in PBMC, lymph nodes, and liver.
Is intramuscular injection of recombinant adeno-associated virus safe and what is its dissemination profile in macaques?
Intramuscular rAAV injection in macaques appears safe over 8-18 months, despite transient viremia and long-term persistence of viral sequences in certain tissues.
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.
Favre et al. (Sat,) reported a other. Recombinant adeno-associated virus (rAAV) injection was evaluated on Dissemination, shedding, long-term persistence in distant organs, and tissue abnormalities. Intramuscular injection of rAAV in macaques appeared safe with no tissue abnormalities at 8 to 18 months, despite transient viremia and persistence of rAAV sequences in PBMC, lymph nodes, and liver.