RNA Silencing in the Struggle against Disease

摘要

Numerous acquired and hereditary diseases are caused by aberrant cellular or microbial gene expression. As a result of sequenc-ing 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 inter-fering 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 eukary-otic 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 tar-get validation. We succeeded in triggering gene silencing by siRNA in prokaryotic cells. This opens promising perspectives regarding valida-tion of prokaryotic gene functions.