The RNA drug revolution -- a new approach to gene therapy

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The RNA drug revolution -- a new approach to gene therapy

http://www.eurekalert.org/pub_releases/2008-01/mali-trd012308.php

RNA interference (RNAi) represents an innovative new strategy for

using small RNA molecules to silence specific genes associated with

disease processes, and a series of review articles describing the

state-of-the-art and potential therapeutic applications of RNAi and

microRNAs will begin with two review papers in the January 2008

issue (Volume 19, Number 1) of Human Gene Therapy, a peer-reviewed

journal published by Ann Liebert, Inc. The papers are available

free online.

At least six clinical trials using RNA interference (RNAi) have been

approved, " with many more coming down the pipeline, " according to

the Editorial by Mark A. Kay, MD, PhD, an Associate Editor of Human

Gene Therapy and the Dennis Farrey Family Professor in Pediatrics

and Professor of Genetics at Stanford University School of

Medicine. " One thing is clear, " adds Kay, " small RNAs as a

therapeutic platform are here to stay. "

The excitement surrounding RNAi and the two main approaches to

delivering RNA-based therapeutics—as mature siRNA molecules or as

short hairpin RNAs (shRNAs)—relates to the discovery of native

microRNA molecules in human cells and their intrinsic ability to

block the expression of a target gene. siRNA therapeutic strategies

in development aim to harness the cells' natural RNAi pathway and

specifically silence a mutant or dysregulated gene.

Traditionally, gene therapy has focused on supplying a normal copy

of a faulty gene, whereas RNAi turns off a problematic gene. These

contrasting approaches share some of the same techniques and

challenges, including delivery of a therapeutic gene or siRNA into

cells.

Human Gene Therapy will publish a series of review papers in four

consecutive issues focusing on a range of topics related to

therapeutic applications of small RNAs. The series begins in the

January issue with a paper entitled, " Behind the Scenes of a Small

RNA Gene-Silencing Pathway, " by Ku, MD, PhD, and

McManus, PhD, from the University of California, San Francisco,

which presents the current understanding of microRNA mechanisms of

action and the potential for applying this knowledge to the

development of RNAi-based treatments.

In the review by Anton McCaffrey, PhD, and Marquez, MA,

entitled, " Advances in Micro-RNAs: Implications for Gene

Therapists, " the authors discuss the likelihood that microRNAs,

which are believed to regulate as many as one-third of all human

gene transcripts (or messenger RNAs), are implicated in many human

diseases. Using gene therapy to manipulate microRNA levels

represents an attractive new approach for controlling gene

expression and identifying targeted and effective therapeutics.

" The concept of using RNA as a therapeutic product is quite

attractive and adds an important new dimension to the field of

nucleic acid based therapeutics including gene therapy. Mark Kay,

Associate Editor of Human Gene Therapy, has organized an exciting

series of reviews summarizing the state of the art of this emerging

field, " says M. , MD, PhD, Editor-in-Chief, and Head of

the Gene Therapy Program, Department of Pathology and Laboratory

Medicine, University of Pennsylvania School of Medicine, in

Philadelphia.