Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi 英文参考文献.docVIP

Minireview Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi Ola Sn?ve Jr*?? and John J Rossi* Addresses: *Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91101, USA. ?Interagon AS, Laboratoriesenteret, NO-7006 Trondheim, Norway. ?Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, NO-7006 Trondheim, Norway. Correspondence: John J Rossi. Email: jrossi@ Published: 29 August 2006 Genome Biology 2006, 7:231 (doi:10.1186/gb-2006-7-8-231) The electronic version of this article is the complete one and can be found online at /2006/7/8/231 ? 2006 BioMed Central Ltd Abstract Short hairpin RNAs can provide stable gene silencing via RNA interference. Recent studies have shown toxicity in vivo that appears to be related to saturation of the endogenous microRNA pathway. Will these findings limit the therapeutic use of such hairpins? RNA interference (RNAi) has loomed large on the scientific radar screen since its discovery nearly a decade ago. Scien- tists have adopted RNAi as the standard tool for sequence- specific silencing of genes and investors have poured money into companies that aim to take advantage of its potential as a severely toxic and 23 resulted in lethality in the mice within two months. Of course, this is not the only apparent setback that RNAi has encountered. The first came when both short interfering RNAs (siRNAs) [2] and shRNAs [3] were shown to trigger immune responses under certain conditions, and many asked whether the hype surrounding RNAi was finally over. Research showed, however, that some of the perceived prob- lems with RNAi-induced nonspecific immune responses could be avoided with proper design - by refraining from using sequences containing certain motifs, for instance (reviewed in [4]). Another che