Antisense oligonucleotide targeting polypyrimidine tract binding protein and use thereof
AssigneeLnctac Co., Ltd.
InventorsHaodong CHEN, Wanwan Li, Grimm MAXIMILIAN, Lina WU, Ting KANG, Lei ZHANG, Chong YUAN
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Abstract
The present disclosure related to antisense oligonucleotide capable of specifically targeting the mRNA sequence of a polypyrimidine tract binding protein 1 (PTBP1) and the use thereof. The antisense oligonucleotide can reduce the expression of PTBP1, thereby treating diseases caused by abnormal expression of the PTBP1 gene.
Claims12
An antisense oligonucleotide (ASO) molecules, wherein the ASO molecules specifically targets polypyrimidine tract binding protein 1 (PTBP1) mRNA at the following positions:
- (1) positions 416-446 of EXON 5;
- (2) positions 692-718 of EXON 7;
- (3) positions 776-815 of EXON 8;
- (4) positions 956-979 of EXON 9;
- (5) positions 1160-1194 of EXON 10/EXON 11;
- (6) positions 1223-1255 of EXON 12;
- (7) positions 1291-1324 of EXON 12/EXON 13;
- (8) positions 1305-1330 of EXON 13;
- (9) positions 1491-1516 of EXON 13/EXON 14;
- (10) positions 1577-1605 of EXON 14/EXON 15;
- (11) positions 1587-1624 of EXON 15;
- (12) positions 2356-2376 of EXON 15 3′UTR;
- wherein the PTBP1 mRNA sequence is as shown in SEQ ID NO:
- 127.
The ASO molecule according to claim 11, wherein the sequence of the ASO molecule is selected from:
- SEQ ID NO:6, 20, 31, 36-41, 55-56, 60, 87, 89, 100-101, 116-119, and 123.
The ASO molecule according to claim 11, wherein the ASO molecule comprises at least one modified nucleotide.
The ASO molecule according to claim 11, wherein all nucleotides in the ASO molecule are 5′-thio-phosphate-linked nucleotides, and the 5′ and 3′ ends each have five nucleotides modified with 2′-O-methoxyethyl (MOE).
A pharmaceutical composition comprising a therapeutically effective amount of an ASO molecules according to claim 11 and a pharmaceutical acceptable excipient;
- wherein the pharmaceutical composition comprises an aqueous gel formulations or an injectable formulation;
- and
- wherein the pharmaceutical composition is formulated for an administration route comprising local, intravenous, intramuscular, subcutaneous, or intradermal.
Use of the ASO molecule according to claim 11 in inhibiting PTBP1 gene expression.
A method of treating a disease caused by abnormal expression of PTBP1 gene, the method comprising administering the ASO molecule according to claim 11 to a subject in need thereof;
- wherein the disease comprises a tumor, Parkinson's disease, Alzheimer's disease, or Huntington's disease.
Dependencies are inferred from the claim text.