MODIFIED HUMAN U1myRNA MOLECULE, GENE CODING THE MODIFIED HUMAN U1myRNA MOLECULE, EXPRESSION VECTOR CONTAINING A GEN, AND THEIR APPLICATION IN GENE THERAPY

摘要

1. A modified human U1myRNA molecule capable of correcting exon skipping caused by a mutation located in a sequence located between 50 base pairs above and 20 base pairs below the exon, the modified human U1myRNA molecule being characterized in that a portion of the single-stranded nucleotide sequence of the 5′-region wild-type human U1myRNA molecules are replaced by a single-stranded binding nucleotide sequence capable of hybridizing with the target nucleotide sequence pre-mRNA transcribed from a target gene of therapeutic interest carrying a mutation that causes an exon skip selected from the group consisting of mutations in a sequence located between 50 base pairs above and 20 base pairs below the exon, the target sequence being located in the region of the pre-mRNA of the target gene located between 2 and 50 base pairs below the portion of the splicing border, the splicing of which is affected by the indicated mutation. 2. The modified human U1myRNA molecule according to claim 1, where the portion of the 5′-region, which is replaced by a binding nucleotide sequence, is from 9 to 20 nucleotides in length. The modified human U1myRNA molecule according to claim 1 or 2, wherein the target gene of therapeutic interest is the coagulation factor IX gene, the SMN2 gene, or the CFTR.4 gene. The modified human U1myRNA molecule according to claim 1, wherein the binding nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10.5. The modified human U1myRNA molecule according to claim 1 for use in the therapeutic treatment of genetic