Academic Journals Database
Disseminating quality controlled scientific knowledge

The dose can make the poison: lessons learned from adverse in vivo toxicities caused by RNAi overexpression

Author(s): Grimm Dirk

Journal: Silence
ISSN 1758-907X

Volume: 2;
Issue: 1;
Start page: 8;
Date: 2011;
Original page

Keywords: RNAi | shRNA | miRNA | viral vector | toxicity | saturation

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.
RPA Switzerland

Robotic Process Automation Switzerland


Tango Jona
Tangokurs Rapperswil-Jona