RU-2026106411-A - Oligonucleotides for modulating KCNT1 expression

Inventors

• ТРАН Элен
• ДАШ ДОРЕС Гийом
• ШАНРИОН Бенжамен

Assignees

• ЛЕ ЛАБОРАТУАР СЕРВЬЕ

Dates

Publication Date

20260508

Application Date

20240814

Priority Date

20230816

Claims (20)

1. 1. An antisense oligonucleotide for reducing the expression of KCNT1, wherein the antisense oligonucleotide has a nitrogenous base sequence that comprises at least 12 consecutive nitrogenous bases of any of the nitrogenous base sequences of SEQ ID NO: 4-12.
2. 2. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide has a nitrogenous base sequence that comprises at least 15 consecutive nitrogenous bases of any one of the nitrogenous base sequences of SEQ ID NO: 4-12.
3. 3. The antisense oligonucleotide of claim 1, wherein the antisense oligonucleotide has a nitrogenous base sequence of any one of SEQ ID NOs: 4-12.
4. 4. The antisense oligonucleotide of claim 3, wherein the antisense oligonucleotide has a nitrogenous base sequence of any one of SEQ ID NOs: 7, 8, and 9.
5. 5. An antisense oligonucleotide according to any one of claims 1 to 4, wherein the antisense oligonucleotide has from 18 to 20 linked nucleosides.
6. 6. An antisense oligonucleotide according to any one of claims 1 to 5, wherein at least one internucleoside linkage is a modified internucleoside linkage.
7. 7. The antisense oligonucleotide of claim 6, wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
8. 8. An antisense oligonucleotide according to claim 7, wherein the phosphorothioate internucleoside linkages are preferably located at positions 1-2, 5-16 and 19-20.
9. 9. An antisense oligonucleotide according to any one of claims 1 to 8, wherein at least one nucleoside of the antisense oligonucleotide comprises a modified sugar moiety.
10. 10. The antisense oligonucleotide of claim 9, wherein the modified sugar moiety comprises a 2'-0-methoxyethyl group.
11. 11. An oligonucleotide having the following formula
12. i) Aes Teo mCeo mCeo mCes Ads Gds Gds Tds Tds Tds Ads mCds mCds mCds Geo Aeo Teo Tes mCe (SEQ ID NO: 7);
13. ii) Tes mCeo mCeo mCeo Aes Gds Gds Tds Tds Tds Ads mCds mCds mCds Gds Aeo Teo Teo mCes Ae (SEQ ID NO: 8);
14. iii) Tes Aeo Teo mCeo mCes mCds Ads Gds Gds Tds Tds Tds Ads mCds mCds mCeo Geo Aeo Tes Te (SEQ ID NO: 9);
15. iv) Aes Teo mCeo mCeo mCes Ads Gds Gds Tds Tds Tds Ads Cds Cds Cds Geo Aeo Teo Tes mCe (SEQ ID NO: 10);
16. v) Tes mCeo mCeo mCeo Aes Gds Gds Tds Tds Tds Ads Cds Cds Cds Gds Aeo Teo Teo mCes Ae (SEQ ID NO: 11);
17. vi) Tes Aeo Teo mCeo mCes Cds Ads Gds Gds Tds Tds Tds Ads Cds Cds mCeo Geo Aeo Tes Te (SEQ ID NO: 12),
18. where A=adenine;
19. C=cytosine;
20. mC=5-methylcytosine;