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10 April 2006

RNAi: A novel antisense technology and its therapeutic potential.

Anne Dallas, Alexander V. Vlassov

Med Sci Monit 2006; 12(4): RA67-74 :: ID: 448934

Abstract

Antisense oligonucleotide agents induce the inhibition of target gene expressionin a sequence-specific manner by exploiting the ability of oligonucleotides to bind to target RNAs viaWatson-Crick hybridization. Once bound, the antisense agent either disables or induces the degradationof the target RNA. This technology may be used for therapeutic purposes, functional genomics, and targetvalidation. There are three major categories of gene-silencing molecules: (1) antisense oligonucleotidederivatives that, depending on their type, recruit RNase H to cleave the target mRNA or inhibit translationby steric hindrance; (2) ribozymes and deoxyribozymes - catalytically active oligonucleotides that causeRNA cleavage; (3) small interfering double-stranded RNA molecules that induce RNA degradation througha natural gene-silencing pathway called RNA interference (RNAi). RNAi is the latest addition to the familyof antisense technologies and has rapidly become the most widely used approach for gene knockdown becauseof its potency. In this mini-review, we introduce the RNAi effect, briefly compare it with existing antisensetechnologies, and discuss its therapeutic potential, focusing on recent animal studies and ongoing clinicaltrials. RNAi may provide new therapeutics for treating viral infections, neurodegenerative diseases,septic shock, macular degeneration, cancer, and other illnesses, although in vivo delivery of small interferingRNAs remains a significant obstacle.

Keywords: Neoplasms - therapy, Neurodegenerative Diseases - therapy, Oligonucleotides, Antisense - genetics, RNA Interference, RNA, Small Interfering - therapeutic use, Virus Diseases - therapy

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750