通过RNA干扰阻断HIV-1复制的基因治疗策略。

Gene therapy strategies to block HIV-1 replication by RNA interference.

作者信息

Herrera-Carrillo Elena, Berkhout Ben

机构信息

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, K3-110 Meibergdreef 15, Amsterdam, 1105 AS, The Netherlands.

出版信息

Adv Exp Med Biol. 2015;848:71-95. doi: 10.1007/978-1-4939-2432-5_4.

DOI:10.1007/978-1-4939-2432-5_4

PMID:25757616

Abstract

The cellular mechanism of RNA interference (RNAi) plays an antiviral role in many organisms and can be used for the development of therapeutic strategies against viral pathogens. Persistent infections like the one caused by the human immunodeficiency virus type 1 (HIV-1) likely require a durable gene therapy approach. The continuous expression of the inhibitory RNA molecules in T cells is needed to effectively block HIV-1 replication. We discuss here several issues, ranging from the choice of RNAi inhibitor and vector system, finding the best target in the HIV-1 RNA genome, alternatively by targeting host mRNAs that encode important viral cofactors, to the setup of appropriate preclinical test systems. Finally, we briefly discuss the relevance of this topic for other viral pathogens that cause a chronic infection in humans.

摘要

RNA干扰（RNAi）的细胞机制在许多生物体中发挥抗病毒作用，可用于开发针对病毒病原体的治疗策略。像由1型人类免疫缺陷病毒（HIV-1）引起的持续性感染可能需要持久的基因治疗方法。需要在T细胞中持续表达抑制性RNA分子以有效阻断HIV-1复制。我们在此讨论几个问题，从RNAi抑制剂和载体系统的选择，在HIV-1 RNA基因组中找到最佳靶点，或者通过靶向编码重要病毒辅助因子的宿主mRNA，到建立合适的临床前测试系统。最后，我们简要讨论该主题与其他导致人类慢性感染的病毒病原体的相关性。