Modified human U1snRNA molecule, a gene encoding for the modified human U1snRNA molecule, an expression vector including the gene, and the use thereof in gene therapy

摘要

A modified human U1snRNA molecule is described, the target sequence of which is located in a region of the pre-mRNA of the target gene comprised between 2 and 50 base pairs downstream of an exon/intron junction site, which is capable of restoring the correct splicing of a target gene of therapeutic interest bearing a mutation which induces exon skipping and resulting in a genetic disease. Modified human U1snRNA molecules are described by way of example for the correction of diseases associated with exon skipping, such as spinal muscular atrophy, hemophilia B, and cystic fibrosis.

主权项

1. A modified human U1snRNA molecule, capable of correcting the skipping of an exon caused by a mutation localized in the sequence comprised between 50 base pairs upstream and 20 base pairs downstream of an exon, the modified human U1snRNA molecule wherein a portion of the single-stranded nucleotide sequence of the 5′ region of the wild-type human U1snRNA is replaced by a single-stranded binding nucleotide sequence, wherein the binding nucleotide sequence is selected from the group consisting of SEQ ID NOs: 1, 2, 51, 52, 53, 54, 55, 56 and 57.