Compounds and methods for modulating interaction between proteins and target nucleic acids

摘要

Provided herein are antisense compounds and methods for recruiting one or more non-cleaving protein to a target nucleic acid in a cell. In certain instances such recruitment of a non-cleaving protein alters the function or activity of the target nucleic acid. In certain such instances, the target nucleic acid a pre-mRNA and the recruitment of the non-cleaving protein results in a change in splicing of the pre-mRNA.

主权项

1. A method of inducing exon skipping in a target pre-mRNA in a cell comprising contacting the cell with an antisense compound comprising a chemically modified oligonucleotide consisting of 18 linked nucleosides; and thereby inducing exon skipping in the pre-mRNA in the cell; wherein the antisense compound comprises:
a 5′-wing region consisting of 2 linked duplex stabilizing nucleosides; a 3′-wing region consisting of 2 linked duplex stabilizing nucleosides; and a central gap region located between the 5′-wing region and the 3′-wing region and consisting of 14 contiguous nucleosides comprising 2′-F modifications;wherein each duplex stabilizing nucleoside is a 2′-methoxyethyl (2′-MOE) nucleoside, andwherein the antisense compound is complementary to an intron of the target pre-mRNA.