Connelly S
Genetic Therapy Inc, 938 Clopper Road, Gaithersburg, MD 20878, USA.
Curr Opin Mol Ther. 1999 Oct;1(5):565-72.
Adenoviral vectors currently represent one of the most efficient means of in vivo hepatocyte gene delivery. Consequently, liver-directed gene transfer has been increasingly explored as a promising approach for the treatment of a diverse range of genetic and acquired diseases. Numerous demonstrations of efficacious adenoviral vector-mediated delivery of a wide array of transgenes in several animal species and humans have been reported. In general, transgene expression was efficient, but transient, in many cases lasting < 1 month. Currently, efforts in the field are focused on the development of highly attenuated adenoviral vectors designed to prolong transgene expression by reducing vector immunogenicity and hepatoxicity. Vector optimization strategies include the development of vectors devoid of all viral coding regions, the generation of chimeric vectors engineered to capitalize on favorable aspects of the component viral systems, the development of tissue-specific regulated gene expression, and the development of strategies to circumvent the host immune system. The use of adenoviral vectors for gene therapy of hereditary, malignant and infectious diseases of the liver, and the vector optimization strategies outlined above are discussed in this work.
腺病毒载体目前是体内肝细胞基因递送最有效的手段之一。因此，肝脏靶向基因转移作为一种治疗多种遗传性和后天性疾病的有前景的方法，已得到越来越多的探索。已有大量报道表明，腺病毒载体在多种动物物种和人类中能有效介导多种转基因的递送。一般来说，转基因表达是有效的，但具有瞬时性，在许多情况下持续时间<1个月。目前，该领域的研究工作集中在开发高度减毒的腺病毒载体，旨在通过降低载体免疫原性和肝毒性来延长转基因表达。载体优化策略包括开发不含所有病毒编码区的载体、构建嵌合载体以利用各组成病毒系统的有利方面、开发组织特异性调控基因表达以及开发规避宿主免疫系统的策略。本文讨论了腺病毒载体在肝脏遗传性、恶性和感染性疾病基因治疗中的应用以及上述载体优化策略。
