INDUCTION OF EXON SKIPPING IN EUKARYOTIC CELLS
First Claim
1. An isolated antisense oligonucleotide of 14 to 40 nucleotides comprising a part of hAON#23 (5′
- -TGGCATTTCTAGTTTGG-3′
(SEQ ID NO;
18)),wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell, said oligonucleotide comprising a modification for increasing its resistance to an endonuclease in a cell.
0 Assignments
0 Petitions
Accused Products
Abstract
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.
59 Citations
25 Claims
-
1. An isolated antisense oligonucleotide of 14 to 40 nucleotides comprising a part of hAON#23 (5′
- -TGGCATTTCTAGTTTGG-3′
(SEQ ID NO;
18)),wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell, said oligonucleotide comprising a modification for increasing its resistance to an endonuclease in a cell. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 16, 18, 20, 21, 22, 25)
- -TGGCATTTCTAGTTTGG-3′
-
2. An isolated antisense oligonucleotide of 14 to 40 nucleotides comprising a part of hAON#24 (5′
- -CCAGAGCAGGTACCTCCAACATC-3′
(SEQ ID NO;
19)), wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell, said oligonucleotide comprising a modification for increasing its resistance to an endonuclease in a cell.
- -CCAGAGCAGGTACCTCCAACATC-3′
-
3. An isolated antisense oligonucleotide of 14 to 40 nucleotides being complementary to a part of exon 51 and comprising a part of hAON#23 (5′
- -TGGCATTTCTAGTTTGG-3′
(SEQ ID NO;
18)), and a part of hAON#24 (5′
-CCAGAGCAGGTACCTCCAACATC-3′
(SEQ ID NO;
19)), wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell, and said oligonucleotide comprising a modification for increasing its resistance to an endonuclease in a cell.
- -TGGCATTTCTAGTTTGG-3′
-
13. A nucleic acid delivery vehicle comprising a transcription unit expressing an antisense oligonucleotide consisting of 14 to 40 nucleotides, said oligonucleotide comprising a part of hAON#23 (5′
- TGGCATTTCTAGTTTGG (SEQ ID NO;
18)), wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell. - View Dependent Claims (17, 19, 23, 24)
- TGGCATTTCTAGTTTGG (SEQ ID NO;
-
14. A nucleic acid delivery vehicle comprising a transcription unit expressing an antisense oligonucleotide consisting of 14 to 40 nucleotides, comprising a part of hAON#24 (5′
- -CCAGAGCAGGTACCTCCAACATC-3′
(SEQ ID NO;
19)), wherein said oligonucleotide induces the skipping of exon 51 of the dystrophin pre-mRNA in a cell.
- -CCAGAGCAGGTACCTCCAACATC-3′
-
15. A nucleic acid delivery vehicle comprising a transcription unit expressing an antisense oligonucleotide consisting of 14 to 40 nucleotides, comprising a part of hAON#23:
- 5′
TGGCATTTCTAGTTTGG (SEQ ID NO;
18) and a part of hAON#24;
;
5′
-CCAGAGCAGGTACCTCCAACATC-3′
(SEQ ID NO;
19), wherein said oligonucleotide induces skipping of exon 51 of the dystrophin pre-mRNA in a cell.
- 5′
Specification