RU-2024133586-A - Oligonucleotide compositions and methods using them

Inventors

• ВАРГИЗ, Чандра
• Мина
• СВРЗИКАПА, Ненад
• МОХАПАТРА, Сусован
• ФРАНСИЗ, Кристофер Дж.
• Вердин, Грегори Л.
• СОКОЛОВСКА, Анна

Assignees

• УЭЙВ ЛАЙФ САЙЕНСЕС ЛТД.

Dates

Publication Date

20260508

Application Date

20241108

Priority Date

20150722

Claims (20)

1. 1. A composition of oligonucleotides with controlled chirality, containing oligonucleotides of a certain type of oligonucleotide, characterized by:
2. 1) the same sequence of bases and length;
3. 2) the same profile of linker groups of the backbone and
4. 3) the same profile of chiral centers of the core;
5. wherein the composition is characterized by controlled chirality in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence and length, with oligonucleotides of a particular oligonucleotide type, wherein the oligonucleotides are targeted to a mutant huntingtin gene and the length is from about 10 to about 50 nucleotides, wherein the backbone linker groups comprise at least one phosphorothioate and wherein the profile of chiral centers of the backbone comprises at least one chiral center of the Rp configuration and at least one chiral center of the Sp configuration.
6. 2. A composition of oligonucleotides with controlled chirality, containing oligonucleotides determined by the presence of:
7. 1) the same sequence of bases and length;
8. 2) the same profile of linker groups of the backbone and
9. 3) the same profile of chiral centers of the backbone, wherein the composition is a substantially pure preparation of a single oligonucleotide in that a predetermined level of oligonucleotides in the composition have the same base sequence and length, the same profile of backbone linker groups and the same profile of chiral centers of the backbone; or a composition of oligonucleotides with controlled chirality, containing oligonucleotides defined by the presence of:
10. 1) the same sequence of bases and length;
11. 2) the same profile of linker groups of the backbone and
12. 3) the same profile of chiral centers of the backbone, wherein the composition is a substantially pure preparation of a single oligonucleotide in that at least about 10% of the oligonucleotides in the composition have the same base sequence and length, the same profile of linker groups of the backbone, and the same profile of chiral centers of the backbone.
13. 3. The composition of claim 1, wherein the oligonucleotides comprise one or more wing regions and a common core region, wherein
14. each wing region is independently two or more bases in length and independently and optionally comprises one or more chiral internucleotide linker groups; and
15. the core region is independently two or more bases in length and independently contains one or more chiral internucleotide linker groups.
16. 4. The composition of claim 1, wherein the oligonucleotides of the oligonucleotide type comprise at least one wing region and a core region, and
17. each wing region is independently two or more bases in length and independently and optionally comprises one or more chiral internucleotide linker groups;
18. the core region is independently two or more bases in length and independently contains one or more chiral internucleotide linker groups; and
19. wherein at least one nucleotide in the wing region differs from at least one nucleotide in the core region, wherein the difference is in one or more of:
20. 1) backbone linker group;