Biology Reference
In-Depth Information
Chapter 1
RNA Interference Pathways and Therapeutic
Exploitation
Jesper B. Bramsen and Thomas B. Hansen
Abstract
RNA interference (RNAi) is currently the method of choice to experimentally
silence endogenous gene expression for functional genomics studies, while ongoing
clinical trials point to its great therapeutic potential. Harnessing endogenous RNAi
pathways to effectuate gene silencing by introducing artificial RNAi substrates or
inhibitors translates into effective silencing efficiencies with high predictability and
reliability but also has the potential to disturb endogenous gene regulation by the
native inhabitants of the RNAi pathway, the microRNAs (miRNAs). A wealth of
RNAi strategies have been developed over the last decade to produce optimal exper-
imental triggers of RNAi entering at all levels in the RNAi pathway. Here we pro-
vide an overview of RNAi silencing pathways and its transformation into a
therapeutic mode using vector-based approaches and chemically optimized, small
interfering RNAs (siRNAs).
1.1
Entering the Age of RNA Interference
Nobel Prizes are rarely awarded based on discoveries <10 years old. Yet, in 2006,
Craig Mellow and Andrew Fire were awarded the Nobel Prize in medicine or physi-
ology for their 1998 discovery of double-stranded RNA-mediated gene silencing by
a process of RNA interference (RNAi) [
1
]. Here a decade later, the impact of this
discovery has been immense; RNAi has opened up completely new research areas,
shed exciting new light on existing research fields, and provided researches with an
unprecedented powerful tool for functional genomics investigations and potential
diagnostic and therapeutic agents.
J. B. Bramsen (
*
) • T. B. Hansen
Department of Molecular Biology and Genetics, Interdisciplinary Nanoscience Center,
Aarhus University , C.F. Mollers Alle , 8000 Aarhus C , Denmark
e-mail: jebb@mb.au.dk
