RNA silencing in the struggle against disease

Abstract

Numerous acquired and hereditary diseases are caused by aberrant cellular or microbial gene expression. As a result of sequencing of the human genome and the genomes of various human pathogens, researchers have gained access to a large number of genes with residual functions. For functional validation of unknown genes, their functions can be specifically inhibited by antisense nucleic acids or small interfering RNAs (siRNAs) and the consequences of the functional loss, that is, the resulting phenotypes, can be analyzed. While antisense nucleic acids block the translation stoichiometrically by docking on the mRNA, siRNAs induce a highly effective cellular mechanism that causes catalytic destruction of several mRNA molecules by a single siRNA molecule. This mechanism, called RNA interference (RNAi), is only intrinsic to eukaryotic cells. Consequently, only eukaryotic target validation is pushed by RNAi whereas time-consuming conventional knockout techniques or the less efficient antisense strategies have to be applied for prokaryotic target validation. We succeeded in triggering gene silencing by siRNA in prokaryotic cells. This opens promising perspectives regarding validation of prokaryotic gene functions. © 2006 New York Academy of Sciences.