Modulation of exon recognition in pre-mRNA by interfering with the secondary RNA structure
The invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre-mRNA.
1. An isolated oligonucleotide of between 20 to 50 nucleotides comprising a sequence consisting of SEQ ID: 27.
2. The isolated oligonucleotide of claim 1 , wherein the oligonucleotide comprises a 2′-O-methyl-phosphorothioate oligoribonucleotide modification.
3. The isolated oligonucleotide of claim 1 , wherein the oligonucleotide is a peptide nucleic acid, locked nucleic acid, and/or morpholino phosphorodiamidate oligonucleotide.