Fink D J, Ramakrishnan R, Marconi P, Goins W F, Holland T C, Glorioso J C
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, PA, USA.
Clin Neurosci. 1995;3(5):284-91.
Herpes simplex virus (HSV) is an attractive candidate vector for treatment of nervous system disease by gene therapy. Here we review molecular aspects of the natural biology of HSV as it relates to vector design and application. Although gene transfer and transient expression was readily achieved using first generation replication defective HSV vectors, these vectors did not provide for long-term transgene expression, a prerequisite for effective treatment of neurodegenerative disease. The principle impediments to effective use of HSV vectors are residual toxicity of non-replicating vectors and the silencing of transgene expression from persisting latent viral genomes in neurons. Recent advances suggest that vectors deleted for multiple immediate early viral genes provide a solution to both of these problems and thereby provide for the first time insight into methods for the effective design of useful gene vectors for central nervous system applications.
单纯疱疹病毒（HSV）是一种极具吸引力的候选载体，可用于通过基因疗法治疗神经系统疾病。在此，我们综述HSV自然生物学的分子层面，因为它与载体设计及应用相关。尽管使用第一代复制缺陷型HSV载体能够轻易实现基因转移和瞬时表达，但这些载体无法实现长期转基因表达，而长期转基因表达是有效治疗神经退行性疾病的一个先决条件。有效使用HSV载体的主要障碍是非复制型载体的残留毒性以及神经元中持续潜伏病毒基因组导致的转基因表达沉默。最近的进展表明，缺失多个立即早期病毒基因的载体为解决这两个问题提供了一种方案，从而首次为中枢神经系统应用有效设计有用基因载体的方法提供了见解。
