期刊
MOLECULAR THERAPY
卷 4, 期 6, 页码 559-566出版社
ACADEMIC PRESS INC
DOI: 10.1006/mthe.2001.0494
关键词
gene therapy; adeno-associated virus; biodistribution; shedding; safety; skeletal muscle; nonhuman primate
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据