METHOD FOR KNOCKING OUT GENE EXPRESSION BY COVALENTLY BINDING ANTISENSE PROBES

摘要

The present invention provides a simple, specific and nontoxic gene knockout method by formation of covalently bonding between modified probes and targeted sequences. When covalently modified first strand probes are hybridized with a second strand of targeted gene transcript, certain modified bases of said first strand will interact with natural bases of said second strand to form covalent bonds by which the translation of said second strand is inhibited. Because the hybridization of said two strands generates covalent base-pairing only between their complementary homology region(s), such specificity increases the targeting efficiency of a gene knockout system. Also, because neither a polymerase extension reaction nor a nuclease digestion can be performed through the covalently bonded region(s) of aforesaid hybrids, the present invention in conjunction with a delivery method can be used to inactivate intracellular function of targeted nucleotide sequences, to inhibit viral infection in vivo and to increase binding stability of antisense drugs in a gene therapy.