Compounds, compositions, methods, and kits relating to telomere extension

Patent metadata

Field	Value
Publication number	US-12053483-B2
Application number	US-202016735684-A
Country	US
Kind code	B2
Filing date	Jan 6, 2020
Priority date	Feb 22, 2013
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

Abstract

Compounds and compositions for the transient expression of exogenous telomerase activity in a cell are provided. The compounds and compositions, which relate to a ribonucleic acid coding for a telomerase reverse transcriptase, are useful in the extension of telomeres in cells needing such treatment. Such cells include, for example, cells that contain shortened telomeres and cells from subjects that may benefit from telomere extension, for example subjects that suffer from, or are at risk of suffering from, age-related or other illnesses. Also provided are methods of extending telomeres through the administration of the provided compounds and compositions to animal cells, either in vitro or in vivo, and kits including the compounds or compositions and instructions for use.

First claim

What is claimed is:

1. A kit for extending telomeres in an animal cell, comprising:
a compound comprising a synthetic ribonucleic acid comprising at least one modified nucleoside and coding for a telomerase reverse transcriptase;
a delivery vehicle; and
instructions for using the compound to extend telomeres in the animal cell;
wherein the telomerase reverse transcriptase is expressed transiently upon administration of the compound to the animal cell.

2. The kit of claim 1 , further comprising packaging materials.

3. The kit of claim 2 , wherein the packaging materials are air-tight.

4. The kit of claim 2 , wherein the packaging materials comprise a metal foil container.

5. The kit of claim 1 , further comprising a desiccant.

6. The kit of claim 1 , further comprising a culture medium.

7. The kit of claim 1 , further comprising an RNase inhibitor.

8. The kit of claim 1 , wherein the compound is sterile.

9. The kit of claim 1 , further comprising: a telomerase RNA component.

10. The kit of claim 9 , wherein the telomerase RNA component is a mammalian, avian, reptilian, or fish telomerase RNA component.

11. The kit of claim 10 , wherein the telomerase RNA component is a human telomerase RNA component.

12. The kit of claim 1 , wherein the delivery vehicle is an exosome, a lipid nanoparticle, a polymeric nanoparticle, a natural or artificial lipoprotein particle, a cationic lipid, a protein, a protein-nucleic acid complex, a liposome, a virosome, or a polymer.

13. The kit of claim 12 , wherein the delivery vehicle is a cationic lipid.

14. The kit of claim 13 , wherein the delivery vehicle is non-immunogenic.

15. The kit of claim 1 , wherein the telomerase reverse transcriptase is a mammalian, avian, reptilian, or fish telomerase reverse transcriptase or a variant that retains telomerase catalytic activity.

16. The kit of claim 15 , wherein the telomerase reverse transcriptase is a human telomerase reverse transcriptase.

17. The kit of claim 1 , wherein the ribonucleic acid comprises a 5′ cap, a 5′ untranslated region, a 3′ untranslated region, and a poly-A tail.

18. The kit of claim 17 , wherein the 5′ cap is non-immunogenic.

19. The kit of claim 17 , wherein the 5′ cap has been treated with phosphatase.

20. The kit of claim 17 , wherein the poly-A tail increases stability of the ribonucleic acid.

21. The kit of claim 17 , wherein the 5′ untranslated region or the 3′ untranslated region comprise a sequence from a stable mRNA or an mRNA that is efficiently translated.

22. The kit of claim 17 , wherein the 5′ untranslated region and the 3′ untranslated region both comprise a sequence from a stable mRNA or an mRNA that is efficiently translated.

23. The kit of claim 17 , wherein the 5′ cap, the 5′ untranslated region, or the 3′ untranslated region stabilizes the ribonucleic acid, increases the rate of translation of the ribonucleic acid, or modulates the immunogenicity of the ribonucleic acid.

24. The kit of claim 1 , wherein the at least one modified nucleoside modulates immunogenicity of the ribonucleic acid.

25. The kit of claim 1 , wherein the synthetic ribonucleic acid is a purified synthetic ribonucleic acid.

26. The kit of claim 25 , wherein the synthetic ribonucleic acid is purified to remove immunogenic components.

27. The kit of claim 1 , wherein the ribonucleic acid codes for a human, cat, dog, mouse, horse, cow, sheep, pig, African elephant, chicken, rat, zebrafish, Japanese medaka, or chimpanzee telomerase reverse transcriptase, or a polypeptide with at least 95% sequence identity to the telomerase reverse transcriptase.

28. The kit of claim 1 , wherein the synthetic ribonucleic acid is formulated in the delivery vehicle.

Assignees

• Univ Leland Stanford Junior

Inventors

• Ramunas John
• Yakubov Eduard
• Blau Helen M
• Cooke John

Classifications

• C12N15/52

  Genes encoding for enzymes or proenzymes · CPC title

• A61K38/45

  Transferases (2) · CPC title

• C12N9/1276

  RNA-directed DNA polymerase (2.7.7.49), i.e. reverse transcriptase or telomerase · CPC title

• C12Y207/07049

  RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase · CPC title

• A61K31/7115 Primary

  Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine · CPC title