Citation

Grimm D. Silence 2011; 2(1): 8.

Copyright

(Copyright © 2011, Holtzbrinck Springer Nature Publishing Group - BMC)

DOI

10.1186/1758-907X-2-8

PMID

22029761

PMCID

PMC3234190

Abstract

For the past five years, evidence has accumulated that vector-mediated robust RNA interference (RNAi) expression can trigger severe side effects in small and large animals, from cytotoxicity and accelerated tumorigenesis to organ failure and death. The recurring notions in these studies that a critical parameter is the strength of RNAi expression and that Exportin-5 and the Argonaute proteins are rate-limiting mammalian RNAi, strongly imply dose-dependent saturation of the endogenous miRNA pathway as one of the underlying mechanisms. This minireview summarizes the relevant work and data leading to this intriguing model and highlights potential avenues by which to alleviate RNAi-induced toxicities in future clinical applications.

Language: en