Smith P G, Oakley F, Fernandez M, Mann D A, Lemoine N R, Whitehouse A
School of Biochemistry & Microbiology, University of Leeds, Leeds, UK.
Gene Ther. 2005 Oct;12(19):1465-76. doi: 10.1038/sj.gt.3302543.
Herpesvirus saimiri (HVS) is capable of infecting a range of human cell types with high efficiency and the viral genome persists as high copy number, circular, nonintegrated episomes which segregate to progeny upon cell division. This allows the HVS-based vector to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Here we assess the dissemination of HVS-based vectors in vivo following intravenous and intraperitoneal administration. Bioluminescence imaging of an HVS-based vector expressing luciferase demonstrates that the virus can infect and establish a persistent latent infection in a variety of mouse tissues. Moreover, the long-term in vivo maintenance of the HVS genome as a nonintegrated circular episome provided sustained expression of luciferase over a 10-week period. A particularly high level of transgene expression in the liver and the ability of HVS to infect and persist in hepatic stellate cells suggest that HVS-based vectors may have potential for the treatment of inherited and acquired liver diseases.
猴疱疹病毒(HVS)能够高效感染多种人类细胞类型,病毒基因组以高拷贝数的环状非整合附加体形式存在,在细胞分裂时可分离至子代细胞。这使得基于HVS的载体能够稳定转导分裂中的细胞群体,并在体外和体内长时间提供持续的转基因表达。在此,我们评估了基于HVS的载体经静脉内和腹膜内给药后在体内的传播情况。对表达荧光素酶的基于HVS的载体进行生物发光成像显示,该病毒可感染多种小鼠组织并建立持续的潜伏感染。此外,作为非整合环状附加体的HVS基因组在体内长期维持,使得荧光素酶在10周内持续表达。肝脏中特别高水平的转基因表达以及HVS感染并在肝星状细胞中持续存在的能力表明,基于HVS的载体可能具有治疗遗传性和获得性肝病的潜力。