Cluster of Excellence CellNetworks, Department of Infectious Diseases-Virology, University of Heidelberg, Heidelberg, Germany.
Prog Mol Biol Transl Sci. 2011;102:165-242. doi: 10.1016/B978-0-12-415795-8.00006-4.
RNA interference (RNAi) is an evolutionarily conserved fundamental cellular mechanism of potent gene and genome regulation whose misfunction is associated with numerous major human pathologies, from metabolic disorders and viral infections to cancers. Over the past 5 years, compelling evidence has been accumulated that this association is provided by dysregulations of specific mi(cro)RNAs and the ensuing aberrant expression of their target genes. Moreover, a string of interesting reports has now added proof that human disorders are also frequently characterized by global alterations in the RNAi machinery, comprising irregular expression and function of the key protein players Drosha, DGCR8, Exportin-5, Dicer, TRBP, and Argonaute. Here, we comprehensively review these emerging findings in the specific contexts of cancers and infections with viral pathogens and, in addition, describe related observations in preclinical gene/RNAi therapy studies. Finally, we also thoroughly discuss the relevance of these results for future basic RNAi research as well as for the looming clinical translation of RNAi-based technologies and therapeutic concepts.
RNA 干扰 (RNAi) 是一种进化上保守的基本细胞机制，能够有效地调节基因和基因组，其功能障碍与许多主要的人类疾病有关，从代谢紊乱和病毒感染到癌症。在过去的 5 年中，大量令人信服的证据表明，这种关联是由特定 microRNAs 的失调以及随之而来的靶基因异常表达提供的。此外，一系列有趣的报告现在也证明，人类疾病通常还伴有 RNAi 机制的全局改变，包括关键蛋白 Drosha、DGCR8、Exportin-5、Dicer、TRBP 和 Argonaute 的表达和功能异常。在这里，我们综合评述了这些在癌症和病毒病原体感染方面的新发现，并在临床前基因/RNAi 治疗研究中描述了相关观察结果。最后，我们还深入讨论了这些结果对未来基础 RNAi 研究以及 RNAi 技术和治疗概念迫在眉睫的临床转化的相关性。
