MEANS AND METHODS FOR MODULATING NOTCH3 PROTEIN EXPRESSION AND/OR THE CODING REGION OF NOTCH3; COMPOSITIONS AND USE THEREOF IN THE TREATMENT OF CADASIL

摘要

PROBLEM TO BE SOLVED: To provide means and a method for modulating NOTCH3 expression and/or protein coding domain.SOLUTION: According to the present invention, there is provided a method for producing mRNA encoding a NOTCH3 protein having EGFL repeats with even numbers of cysteine residues from a pre-mRNA encoding a mutant NOTCH3 protein having an EGFL repeat with an uneven number of cysteine residues. The method comprises providing a cell expressing the pre-mRNA with an anti-sense oligonucleotide that is complementary to and hybridizes with the pre-mRNA and that thereby induces the exclusion of exon 4 and exon 5 from mRNA produced from the pre-mRNA. In the method, the EGFL-repeat with an uneven number of cysteines is encoded by exon 4 and/or exon 5.SELECTED DRAWING: Figure 1