GENE EXPRESSION INHIBITION AND USES THEREOF

摘要

The present invention relates to methods and compositions for inhibiting gene expression in a cell or organism, as well as uses thereof. More particularly, the invention is based on the conception and design of selective and efficient inhibitory oligonucleotides that are expressed in cells in the presence of an RNA polymerase. The method thus preferably utilizes a (recombinant) cell or a non-human (transgenic) organism expressing a single­subunit RNA polymerase and a molecule comprising a sequence encoding an expression­inhibiting oligonucleotide specific for a targeted gene operably linked to element(s) allowing transcription of said sequence by the single-subunit RNA polymerase in said cell or organism. Preferably, the expression-inhibiting oligonucleotide transcribed by the cells is an antisense RNA, a siRNA, a shRNA or a ribozyme. The present invention also relates to the use of this gene expression inhibition system for identifying/studying the function of a targeted gene, for validating a therapeutic target, or for optimizing an expression­ inhibiting oligonucleotide. The present invention further relates to a kit for implementing this gene expression inhibition system.