Processing

Please wait...

Settings

Settings

Goto Application

1. WO2019055460 - COMPOSITIONS AND METHODS FOR TREATING TRANSPOSON ASSOCIATED DISEASES

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

What is claimed is:

1. One or more antisense oligonucleotides complementary to a transposable element present in an intronic sequence within a genome.

2. The antisense oligonucleotide of claim 1, wherein the transposable element is a retrotransposon.

3. The antisense oligonucleotide of claim 1, wherein the retrotransposon is a long interspersed nuclear element-1 (LINE-1), an Arthrobacter luteus element (Alu), short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR-Alu) or (SVA), or an endogenous retrovirus (ERV).

4. The antisense oligonucleotide of claim 1, wherein the oligonucleotide comprises a modified backbone.

5. The antisense oligonucleotide of claim 4, wherein the modified backbone comprises a 2'methoxy ethyl modification or a 2' O-methyl modification.

6. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide binds a splice acceptor site present in the SVA or Alu sequence.

7. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide comprises or consists of a sequence listed in Table 1.

8. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

9. The antisense oligonucleotide of claim 8, wherein the modified sugar moiety is a 2 -0-methyl group or a 2'-0-methoxyethyl group.

10. The antisense oligonucleotide of claim 1, wherein said nucleobase oligomer comprises at least one modified nucleobase.

11. The antisense oligonucleotide of claim 1, wherein said oligonucleotide comprises DNA residues, RNA residues, modified DNA or RNA residues, or combinations of any of these.

12. The antisense oligonucleotide of claim 1, wherein said transposable element inserts into an intronic sequence that is upstream, downstream, or within a gene of interest.

13. A set of antisense oligonucleotides comprising 2 or more of the antisense

oligonucleotides of claims 1-11.

14. The set of claim 13, wherein the set comprises 2-50 antisense oligonucleotides.

15. A pharmaceutical composition comprising an effective amount of the antisense oligonucleotide of claims 1-11 or the set of claims 12-14 in a pharmaceutically acceptable excipient.

16. A method for treating a subject having a genetic disorder associated with the insertion of a transposable element, the method comprising administering to the subject one or more antisense oligonucleotides of any of the preceding claims.

17. A method for treating a subject having a genetic disorder associated with the insertion of a transposable element, the method comprising administering to the subject one or more antisense oligonucleotides that binds to the transposable element or to a sequence present in a flanking region.

18. The method of claim 17, wherein the oligonucleotide binds upstream or downstream of the transposable element.

19. The method of claim 16, wherein the transposable element is a retrotransposon.

20. The method of claim 16, wherein the retrotransposon is a long interspersed nuclear element-1 (LINE-1), an Arthrobacter luteus element (Alu), a short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR-. 1/w) or (SVA), or an endogenous retrovirus (ERV).

21. The method of claim 16, wherein the subject is heterozygous for a mutation associated with a genetic defect.

22. The method of claim 16, wherein the subject comprises a first allele comprising a genetic mutation and a second allele comprising a retrotransposon insertion.

23. An isolated cell that is heterozygous for a mutation associated with a genetic defect, comprising a genetic mutation and a second allele comprising a retrotransposon insertion.

24. The cell of claim 23, wherein the retrotransposon is a long interspersed nuclear element-1 (LINE-1), an Arthrobacter luteus element (Alu), a short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR- 4/«) or (SVA), or an endogenous retrovirus (ERV).

25. The cell of claim 23 or 24, wherein the cell is a fibroblast.

26. A method of identifying an agent that inhibits a splicing event caused by a

retrotransposon insertion, the method comprising contacting the cell of any one of claims 24-25, and detecting a splice product that does not comprise a retransposon sequence or fragment thereof.

27. The method of claim 26, wherein the retrotransposon is a long interspersed nuclear elements-1 (LINE-1), an Arthrobacter luteus element (Alu), a short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR- 4/«) or (SVA), or an endogenous retrovirus (ERV).