38] Antisense RNA inhibition of endogenous genes

Abstract

Regulation of gene expression by antisense inhibition was first described as a natural prokaryotic control mechanism. Studies suggest that with this vector and host combination, there are no effective differences between the ability of antisense genomic fragments or cDNA constructs to inhibit HPRT synthesis. The ratio of antisense RNA to endogenous sense RNA needed for inhibition is unknown and may vary from system to system; certainly the specific mechanism of inhibition affects this ratio. Tissue-specific variations in the rates of transcription, hnRNA processing, and message degradation, as well as the amount of inhibition required for phenotypic alteration, may similarly influence the optimal conditions for useful antisense inhibition. Antisense techniques may yield information about the functional role of many expressed sequences which are currently uncharacterized. In conjunction with transgenic mouse techniques, antisense inhibition may offer a unique opportunity to study the pathophysiologic significance of metabolic imbalances, and their consequences on development and morphogenesis. A better understanding of the specific mechanisms of inhibition and improvements in our abilities to deliver antisense DNA and RNA will be important in making this technique applicable to a wide range of organisms.