Delivering siRNA <span class='italic'>in vivo</span> for functional genomics and novel therapeutics

doi:10.1017/CBO9780511546402.025

22 - Delivering siRNA in vivo for functional genomics and novel therapeutics

Published online by Cambridge University Press: 31 July 2009

Patrick Y. Lu and

Martin C. Woodle

Edited by

Krishnarao Appasani

Foreword by

Andrew Fire and

Marshall Nirenberg

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Patrick Y. Lu: Affiliation:
Intradigm Corporation
Martin C. Woodle: Affiliation:
Intradigm Corporation
Krishnarao Appasani: Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire: Affiliation:
Stanford University, California

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Summary

Introduction

Use of siRNA in vivo to down regulate expression of a specific gene requires knowledge of target sequence accessibility, target tissue deliverability, and, for most applications, siRNA stability in both extracellular and intracellular environments (McManus and Sharp, 2002). Unlike in vitro transfection of siRNA into cells, in vivo delivery of siRNA into targeted tissue of animal models is much more complicated, involving physical, chemical and biological approaches, and in some cases their combination (Lu et al., 2003). A consequence of the fast-growing literature on using siRNA as a research tool for functional genomics is an emerging interest in siRNA as a therapeutic. Therapeutic applications, however, clearly depend upon optimized local and systemic delivery of siRNA in vivo. Therefore, delivering siRNA into targeted tissues and maintaining its activity within targeted cells and on the targeted gene sequence are the key aspects considered here, in order to fulfill the goals of both functional genomic research and therapeutic development.

Currently, using siRNA to characterize gene function and to explore therapeutic potential is spreading over almost every field in biomedical research. This phenomenon results from two basic realities: 1) siRNA is proving to be a very potent, robust, and easy to use inhibitor activated by a natural process and 2) down regulation of individual genes is a powerful tool for understanding their biological functions and may generate therapeutic benefits by reversing the pathological effects caused by over-expression of those genes.

Type: Chapter
Information: RNA Interference Technology
From Basic Science to Drug Development
, pp. 303 - 317

DOI: https://doi.org/10.1017/CBO9780511546402.025 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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