中文摘要：

重组腺相关病毒 （rAAV） 因具有在体内可以长期稳定表达转基因、安全性高等优点, 迅速成为基因治疗的首选载体之一。最近采用 rAAV 基因药物进行的血友病临床实验所暴露的细胞免疫毒性引起人们高度关注, 此问题能否顺利解决直接关系该类药物的发展前景。之后的研究发现针对 AAV 衣壳蛋白的 T 细胞免疫反应是毒性反应的原因。本文针对 rAAV 细胞免疫毒性的各种假说进行了分析, 总结了 AAV 衣壳蛋白抗原肽如何在靶细胞递呈并激活细胞毒性 T 淋巴细胞的研究结果, 并针对该免疫毒性的各关键环节提出了可能的解决方案, 包括免疫抑制、载体优化、提高纯度等, 期望有助于提高 rAAV 基因药物的临床安全性和有效性。

英文摘要：

Gene medicine based on recombinant adeno-associated virus （rAAV） vector has rapidly become the prior-choose reagent for gene therapy, since it had been shown that the rAAV was able to stably express many genes in vivo without detectable side-effect. However, recent findings of CTL immune responses to AAV capsid in a clinical trial highlighted a new issue regarding safety that previously was not identified in animal studies. Obviously it is so important to understand the interaction of rAAV with the immune system in details for the safety and success of rAAV gene medicine. In this review we evaluate several current hypotheses aiming to explain the cellular immunotoxicity, also analysis the current findings including the presentation kinetics of the capsid antigen and the activation of CTL. Focusing on the key steps of the immune response several solutions are proposed, including immunosuppression, optimization of vector and improvement of purity, in order to insure clinical safety and efficacy of rAAV.