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AssigneeASOcura Pharmaceuticals Suzhou Co., Ltd.
InventorsYimin Hua, Pengchao Feng
Estimating the term…
Provided are novel antisense oligonucleotides (“ASOs”) that generate or promote exon skipping during pre-mRNA splicing, pharmaceutical compositions containing such ASOs, and their use. ASOs (e.g., bipartite ASOs) comprise a targeting sequence and a 5′-splice-site decoy sequence operably connected at the 5′ and/or 3′end of the targeting sequence. The decoy sequence may have 5, 6, 7, 8, 9, 10, 11, 12 or 13 nucleotides in length, a portion of which is complementary to the single-strand 5′end of U1 snRNA. The targeting sequence hybridizes to a targeted region, such as an exon of interest, a flanking intron sequence upstream or downstream of the exon of interest, or an intron-exon junction upstream or downstream of the exon of interest.
An oligonucleotide comprising or consisting of a targeting sequence, and a 5′-splice-site decoy sequence operably connected at the 5′ end and/or 3′ end of the targeting sequence:
The oligonucleotide of any one of the prior claims, the exon of interest being selected from the group consisting of exon 7 of the endogenous SMN1 and SMN2 genes, exons 45, 51 and 52 of the endogenous DMD gene, exon 17 of the endogenous APP gene, exon 41 of the endogenous CEP290 gene, exon 19 of the endogenous HER2 gene, exon 10 of the SCA3 gene, exon 10 of the endogenous PKM gene, and exon 6 of the endogenous MDM4 gene.
The oligonucleotide of any one of the prior claims, the targeting sequence comprising or consisting of a nucleotide sequence selected from the group consisting of the nucleotide sequences of SEQ ID Nos. 25, 29, 33, 37, 41, 45, 49, 75, 92, 124, 156, 188, 220, 252, 284, and 316.
The oligonucleotide of any one of the prior claims, the targeting sequence being linked to the decoy sequence directly.
The oligonucleotide of any one of the prior claims, comprising at least one nucleotide analog, e.g., without limitation, selected from the group consisting of 2′-O-methoxyethyl-modified oligonucleotides with phosphodiester or phosphorothioate backbone, and phosphorodamidate morpholino oligomers.
A composition comprising the oligonucleotide of any one of the prior claims and a pharmaceutically acceptable carrier.
A vector encoding the oligonucleotide of any one of the prior claims.
Dependencies are inferred from the claim text.