Wolfe J H, Deshmane S L, Fraser N W
School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Nat Genet. 1992 Aug;1(5):379-84. doi: 10.1038/ng0892-379.
Genetic disorders affecting the central nervous system (CNS) can potentially be treated by gene transfer using vectors which infect and express genes in post-mitotic neurons. Herpesviruses establish latent infections in neurons during which only one viral gene (LAT) is expressed, thus the LAT promoter may express foreign genes in latently infected CNS cells. Expression of a beta-glucuronidase gene driven by the LAT promoter was tested in mice lacking this enzyme, which are a model for a human genetic disease affecting the CNS (mucopolysaccharidosis VII, Sly disease). Cells expressing the missing enzymatic activity were present in the trigeminal ganglia and brainstems of latently infected animals, up to four months post-inoculation, demonstrating the potential of this approach for the long-term expression of foreign genes in the CNS.
影响中枢神经系统（CNS）的遗传疾病有可能通过基因转移来治疗，所使用的载体可在有丝分裂后的神经元中感染并表达基因。疱疹病毒在神经元中建立潜伏感染，在此期间仅表达一个病毒基因（LAT），因此LAT启动子可能在潜伏感染的中枢神经系统细胞中表达外源基因。在缺乏这种酶的小鼠中测试了由LAT启动子驱动的β-葡萄糖醛酸酶基因的表达，这些小鼠是一种影响中枢神经系统的人类遗传疾病（粘多糖贮积症VII型，斯利氏病）的模型。在潜伏感染动物的三叉神经节和脑干中存在表达缺失酶活性的细胞，接种后长达四个月，这证明了这种方法在中枢神经系统中长期表达外源基因的潜力。
