INDUCTION OF EXON SKIPPING IN EUKARYOTIC CELLS

摘要

The present invention provides a method for at least in part decreasing the production of an aberrant protein in a cell, the cell comprising pre-mRNA comprising exons coding for the protein, by inducing so-call exon skipping in the cell. Exon-skipping results in mature mRNA that does not contain the skipped exon, which leads to an altered product of the exon codes for amino acids. Exon skipping is performed by providing a cell with an agent capable of specifically inhibiting an exon inclusion signal, for instance, an exon recognition sequence, of the exon. The exon inclusion signal can be interfered with by a nucleic acid comprising complementarity to a part of the exon. The nucleic acid, which is also herewith provided, can be used for the preparation of a medicament, for instance, for the treatment of an inherited disease.

主权项

1. An isolated antisense oligonucleotide 17 to 40 nucleotides in length comprising a nucleotide sequence capable of binding to a purine-rich sequence of exon 51 of the human dystrophin pre-mRNA and inducing skipping of exon 51 of said pre-mRNA in a human muscle cell, wherein hAON#23: 5′-TGGCATTTCTAGTTTGG-3′ (SEQ ID NO: 18) binds to said purine-rich sequence and causes skipping of exon 51 of said pre-mRNA in a human muscle cell, said antisense oligonucleotide comprising a modification for increasing its resistance to an endonuclease in a cell.