Hackett N R, Kaminsky S M, Sondhi D, Crystal R G
Belfer Gene Therapy Core Facility, Weill Medical College of Comell University, 520 East 70th Street, ST 505, New York, NY 10021, USA.
Curr Opin Mol Ther. 2000 Aug;2(4):376-82.
Current viral gene therapy vectors effectively transfer genes in vivo at the price of eliciting innate and acquired host responses against the vector and/or transgene. Antigens present in the viral vector and the expression of the transgene both cause cellular and humoral immune responses dependent on the viral vector, the route of administration, and the genotype and infection history of the host. In general, adenoviral vectors cause strong immune responses, which result in only transient expression of the therapeutic gene. Adeno-associated virus and retrovirus vectors elicit weaker immune responses and can therefore result in long-term gene transfer and expression. Methods to avoid host responses, including modification of viral vector and immunosuppression of the host, can increase the longevity and efficiency of gene transfer.
当前的病毒基因治疗载体能够有效地在体内转移基因，但其代价是引发宿主针对载体和/或转基因的先天性和获得性免疫反应。病毒载体中存在的抗原以及转基因的表达都会引发细胞免疫和体液免疫反应，这些反应取决于病毒载体、给药途径以及宿主的基因型和感染史。一般来说，腺病毒载体引发强烈的免疫反应，这导致治疗基因只能短暂表达。腺相关病毒和逆转录病毒载体引发的免疫反应较弱，因此可以实现长期的基因转移和表达。避免宿主免疫反应的方法，包括对病毒载体进行修饰以及对宿主进行免疫抑制，可以提高基因转移的持久性和效率。
