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Gene transfer to the nervous system using HSV vectors

机译：使用HSV载体将基因转移到神经系统

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The natural history of Herpes simplex virus type 1 (HSV-1) infection in humans suggests its potential for development as a gene transfer vehicle suitable for nervous system applications. HSV-1 has a broad host range, does not require cell division for infection and gene expression and has evolved to persist in a life-long nonintegrated latent state without the expression of viral proteins or evidence of neurodegenerative disease in the immune competent host. The virus also has evolved a unique neuronal-specific promoter system that remains active during latency and fortuitously may be used to express therapeutic proteins without compromising the latent state. The establishment of latency also does not require the expression of viral lytic functions and thus removal of genes required for expression of the viral cascade of expressed products allows for safe vector design without the possibility of reactivation from latency. The HSV-1 genome is 152 Kb in length and of the 84 known genes (Roizman & Sears, 1996), approximately half are dispensable for virus replication in cell culture thereby providing considerable opportunity for introduction of foreign sequences. In this review, a brief overview of the biology of HSV relevant to vector design and progress in reducing virus cytotoxicity and its relevance to the level and duration of transgene expression is discussed. Methods for the expression of transgenes in the peripheral and central nervous system using the latency active promoters are described and strategies are suggested for potential applications to the treatment of neurodegenerative disease and cancer.
机译：人类单纯疱疹病毒1型（HSV-1）感染的自然历史表明，它有可能发展成为适合神经系统应用的基因转移载体。 HSV-1具有广泛的宿主范围，不需要细胞分裂即可进行感染和基因表达，并且已经进化成可以维持终生的非整合潜伏状态，而无需在免疫感受态宿主中表达病毒蛋白或出现神经退行性疾病。该病毒还进化出了独特的神经元特异性启动子系统，该系统在潜伏期保持活跃，并且可以偶然用于表达治疗性蛋白质而不会损害潜伏状态。潜伏期的建立也不需要表达病毒裂解功能，因此去除表达表达产物的病毒级联反应所需的基因可以进行安全的载体设计，而没有从潜伏期重新激活的可能性。 HSV-1基因组的长度为152 Kb，在84个已知基因中（Roizman＆Sears，1996），大约一半可用于细胞培养中的病毒复制，从而为引入外源序列提供了可观的机会。在这篇综述中，讨论了与载体设计有关的HSV生物学的简要概述以及在减少病毒细胞毒性方面的进展及其与转基因表达水平和持续时间的相关性。描述了使用潜伏期活性启动子在外周和中枢神经系统中表达转基因的方法，并提出了潜在的治疗神经退行性疾病和癌症的策略。

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