重组腺相关病毒载体的免疫性研究及其解决策略

摘要/Abstract

摘要： 重组腺相关病毒载体(rAAV)作为一种高靶向性和良好安全性的病毒载体,在基因治疗的临床前和临床研究中具有极广泛的应用前景。目前在全球范围内已有71项临床研究在进行之中或已经完成。其中有相当部分在血友病、视网膜疾病、帕金森、囊性纤维化以及癌症等疾病的治疗中都取得了显著疗效。随着临床上的成功,人们对rAAV所引起的免疫性及其应对策略也进行了更为广泛而深入的研究。本文将就rAAV的外壳蛋白以及目的基因产物所引起的免疫性进行综合探讨,并结合我们的部分研究工作从改变外壳蛋白、给药方式以及消除内源性外壳蛋白的表达等方面对消除外壳蛋白所引起的免疫性的一些策略加以详述。

Abstract: Recombinant adeno-associated viral vectors (rAAV) have been demonstrated as a significant promising viral vector for human gene therapy based on its high safety and good targeting activity in preclinical tests and clinical trials, and there are 71 clinical trials have dong or been doing. Part of them have gain an excellent success in the mant with Hemophilia, retinal disease, Parkinson's disease, cystic fibrosis, cancer et al. With the success in clinical trials, people process a series extensive and deeply research with the immunity induced by rAAV and the responding strategy respond to. In this review we systematically analyze the immunity caused by capsid and transgene product. Apart from this, some strategies, partly based on our work, to eliminate the immunity caused by capsid such as change the capsid, administration route, and eliminate the expression of endo-capsid are reviewed as well.

Key words: Recombinant adeno-associated viral vectors, Immunity, Capsid, Transgene product, Endo-capsid

中图分类号:

卢超, 万江波, 唐明清, 肖卫东, 许瑞安. 重组腺相关病毒载体的免疫性研究及其解决策略[J]. 中国临床药理学与治疗学, 2010, 15(5): 577-583.

LU Chao, WAN Jiang-bo, TANG Ming-qing, XIAO Wei-dong, XU Rui-an. Immunity and strategy to recombinant adeno-associated virus vector[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(5): 577-583.

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