Philipps-University, School of Medicine, Department of Pharmacology and Toxicology, Marburg, Germany.
Expert Opin Biol Ther. 2009 Dec;9(12):1533-42. doi: 10.1517/14712590903307354.
RNA interference (RNAi) represents a powerful mechanism for the knockdown of any target gene of interest. It is based on the action of small double-stranded RNA molecules (siRNAs) which are complementary to the target sequence. Crucial for the induction of RNAi, particularly for any therapeutic in vivo applications, is the delivery of siRNAs or small hairpin RNA (shRNA)-encoding DNA constructs. Extending the portfolio of viral or non-viral strategies, bacteria have been shown to be able to deliver shRNA-encoding DNA into tumor cells. In a process termed 'transkingdom RNA interference' (tkRNAi), the genetically modified bacteria themselves produce shRNAs which, upon bacterial infection, become available for the target cells for further processing and induction of RNAi. In 'bacteria-mediated RNAi' (bm-RNAi), the bacteria only deliver the shRNA-encoding DNA construct with subsequent transcription of the shRNA in the target cells. This review briefly discusses general aspects of the RNAi mechanism and various delivery systems, and then describes tkRNAi and bm-RNAi in the context of therapeutic applications.
RNA 干扰 (RNAi) 代表了一种强大的机制，可以降低任何目标基因的表达。它基于小双链 RNA 分子（siRNA）的作用，这些分子与目标序列互补。对于诱导 RNAi 至关重要的是，特别是对于任何体内治疗应用，siRNA 或短发夹 RNA (shRNA) 编码 DNA 构建体的递送。扩展病毒或非病毒策略的组合，已经表明细菌能够将 shRNA 编码的 DNA 递送至肿瘤细胞中。在称为“跨域 RNA 干扰”(tkRNAi) 的过程中，经过基因改造的细菌本身产生 shRNA，当细菌感染时，这些 shRNA 可用于靶细胞进行进一步加工和 RNAi 的诱导。在“细菌介导的 RNAi”(bm-RNAi) 中，细菌仅递送至 shRNA 编码的 DNA 构建体，随后在靶细胞中转录 shRNA。这篇综述简要讨论了 RNAi 机制和各种递送系统的一般方面，然后描述了 tkRNAi 和 bm-RNAi 在治疗应用方面的情况。
