Antisense oligonucleotides which combat aberrant splicing and methods of using the same

摘要

A method of blocking a splicing process in a pre-mRNA molecule is disclosed. The splicing process is mediated by splicing factors and the pre-mRNA molecule contains a set of splice elements which bind the splicing factors and define an intron which is removed by splicing to produce a mRNA molecule encoding a native protein. The method comprises hybridising an antisense oligonucleotide to the pre-mRNA molecule to create a duplex molecule under conditions which permit splicing. The antisense oligonucleotide is one which does not activate RNase H, and is selected to block a member of the splice elements so that the binding and/or function of the splicing factors which mediate the splicing process is disrupted.