Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting

N.   K.   Sahu; G.      Shilakari; A.      Nayak; D.   V.   Kohli

doi:10.2174/138920107782109985

Abstract

This review deals with the antisense technology that, together, forms a very powerful tool to inhibit gene expression and may be used for studying gene function (functional genomics) and for therapeutic purpose (antisense gene therapy). Antisense oligonucleotides block translation of target mRNAs in a sequence specific manner, either by steric blocking of translation or by destruction of the bound mRNA via RNase-H enzyme. For proper designing, accessible sites of the target RNA for binding antisense oligonucleotides have to be identified. Whether being used as an experimental reagent or pharmaceuticals, several problems or drawbacks have to be overcome for successful applications. Toward this direction, various modifications of sugar, bases and phosphate backbone of antisense oligonucleotides have been attempted. In recent years valuable progress has been achieved through the development of advanced cellular delivery systems and novel chemically modified nucleotides with improved properties such as enhanced serum stability, higher target affinity and low toxicity. These qualities and the specificity of binding make this technique a potentially powerful therapeutic tool for gene targeting and/ or expression regulation. This review discusses the basis of structural design, mode of action, chemical modification, enhanced cellular uptake, therapeutic application and future possibilities in the field of advanced antisense technology.

Keywords: Oligonucleotides, antisense oligonucleotides, antisense technology, siRNA, triplex forming oligonucleotides, phosphorothioate, ribozyme, RNase H