Inhibition of polyomavirus replication
AssigneeAcademisch Ziekenhuis Leiden (H.O.D.N. Lumc)
InventorsEric Peter VAN DER VEER, Anton Jan VAN ZONNEVELD, Jurriën PRINS
Life of this patent
Estimating the term…
Abstract
The invention relates to antisense molecules and methods for modulating splicing of polyomavirus T antigen pre-mRNA. In one aspect the invention relates to an antisense oligonucleotide 12 to 30, preferably 17, 18, 19 or 20 to 30 nucleobases in length which comprises a sequence that is the reverse complement of a contiguous stretch of at least 12 nucleobases of a polyomavirus T-antigen pre-mRNA and which antisense oligonucleotide can modulate splicing of said T-antigen pre-mRNA in a cell.
Claims20
1-14. (canceled)
A method of treatment of a polyomavirus infection in a subject, the method comprising administering to the subject a single stranded (ss) RNA antisense oligonucleotide of 18 to 30 ribonucleotides in length comprising a sequence that is a reverse complement of a contiguous stretch of at least 18 nucleobases of a polyomavirus T-antigen pre-mRNA, wherein the ssRNA antisense oligonucleotide comprises a modification capable of rendering an RNA duplex resistant to the action of RNase H, wherein the RNA duplex is formed by the ssRNA antisense oligonucleotide and the T-antigen pre-mRNA, wherein ssRNA antisense oligonucleotide is capable of modulating splicing of said T-antigen pre-mRNA in a cell, and wherein:
- the ssRNA antisense oligonucleotide is directed towards the splice donor site of exon 1, wherein the oligonucleotide comprises one or more nucleobases targeting exon 1 and one or more nucleobases targeting the corresponding intronic region of said splice donor at exon 1, or
- the ssRNA antisense oligonucleotide is directed towards the splice acceptor site of exon 2, wherein the oligonucleotide comprises one or more nucleobases targeting exon 2 and one or more nucleobases targeting the corresponding intronic region of said splice acceptor at exon 2.
Dependencies are inferred from the claim text.