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Current Medicinal Chemistry - Central Nervous System Agents

Editor-in-Chief

ISSN (Print): 1568-0150
ISSN (Online): 1875-6158

DNA and RNA Code-reading Molecules as Potential Gene Silencers in Neurobiology- What are They and what are They Good for?

Author(s): Marcella Faria, Carine Giovannangeli and Henning Ulrich

Volume 4, Issue 4, 2004

Page: [243 - 253] Pages: 11

DOI: 10.2174/1568015043356904

Price: $65

Abstract

The selective silencing of a targeted gene is the ultimate goal of most strategies developed for functional studies in basic sciences and/or for drug development. Gene expression has at least three different polymeric molecules as intermediates of information processing; the gene itself, the corresponding mRNA and the polypeptide it codes for. In the present review we will focus on antigene molecules, namely triplex forming-molecules (TFMs), polyamides and designed zinc finger proteins (ZFPs) as means to achieve gene targeting, and on double-stranded RNAs (dsRNA) as means to achieve RNA interference. These two strategies are not the most frequently used, double gene knock-outs by homologous recombination tends to be preferred as antigene strategy, and antisense agents have been more extensively used when the mRNA was to be targeted. Nevertheless, some considerations regarding the specificity of antigene molecules and dsRNAs for their targets, as well as the need of relatively small and stable molecules for the triggering of selective inhibition in both cases, and no major constraints regarding the cell types they should be delivered to, emphasize their potential as gene function modulators. Pathological conditions in the nervous system can result from the malfunction of a variety of proteins, most frequently in degenerative diseases hyper stimulation or overexpression of receptors or enzymes is observed. In these particular cases, the development of efficient and specific inhibitors of gene function would be an approach of choice. Moreover, it was recently demonstrated that RNA i can be triggered in embryonic carcinoma (EC) cell lines, an accepted model for neuronal development.


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