跨界RNA干扰（tkRNAi）：一种诱导治疗性基因沉默的新方法。

Transkingdom RNA interference (tkRNAi): a novel method to induce therapeutic gene silencing.

作者信息

Nguyen Thu A, Fruehauf Johannes H

机构信息

Harvard Medical School, Gl Cancer Laboratory, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

出版信息

Methods Mol Biol. 2009;514:27-34. doi: 10.1007/978-1-60327-527-9_3.

DOI:10.1007/978-1-60327-527-9_3

PMID:19048211

Abstract

RNA interference is a phenomenon in which specific, endogenous genes are silenced by mRNA degradation. This technology is highly regarded as a potential therapeutic due to its high efficacy and low toxicity. However, the difficulty of delivering RNAi to target cells has impeded the development of RNAi-based therapies. One method to overcome this barrier is the use of a nonpathogenic bacteria vector, Escherichia coli, to deliver RNAi to target cells with high efficacy. In transkingdom interference RNAi (tkRNAi) delivery, E. coli were engineered to transcribe short RNA (shRNA) from a plasmid (TRIP) containing the invasin gene Inv and the listeriolysin O gene Hly. tkRNAi is successful in eliciting efficient gene silencing in vitro and in vivo.

摘要

RNA干扰是一种特定的内源性基因通过mRNA降解而沉默的现象。由于其高效性和低毒性，这项技术被高度视为一种潜在的治疗方法。然而，将RNA干扰递送至靶细胞的困难阻碍了基于RNA干扰疗法的发展。克服这一障碍的一种方法是使用非致病性细菌载体大肠杆菌，将RNA干扰高效地递送至靶细胞。在跨界干扰RNA干扰（tkRNAi）递送中，对大肠杆菌进行工程改造，使其从含有侵袭素基因Inv和溶血素O基因Hly的质粒（TRIP）转录短RNA（shRNA）。tkRNAi在体外和体内均成功引发了有效的基因沉默。