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

Patent metadata

Field	Value
Publication number	US-10525075-B2
Application number	US-201414187265-A
Country	US
Kind code	B2
Filing date	Feb 22, 2014
Priority date	Feb 22, 2013
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

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 method of extending telomeres, comprising the step of:
administering a compound to an animal cell wherein said administering is in vitro,
wherein the compound comprises a synthetic ribonucleic acid comprising at least one modified nucleoside and coding for a telomerase reverse transcriptase,
wherein the telomerase reverse transcriptase is expressed transiently in the cell, and
wherein at least one telomere is extended within the cell.

2. The method of claim 1 , wherein the cell has at least one shortened telomere prior to the administering step.

3. The method of claim 1 , wherein the cell is from or in a subject suffering from or at risk of an age-related illness, an age-related condition, or an age-related decline in function or appearance.

4. The method of claim 1 , wherein the cell is from or in a subject suffering from or at risk of cancer, heart disease, stroke, diabetes, diabetic ulcers, Alzheimer's disease, osteoporosis, a decline in physical ability or appearance, physical trauma or chronic physical stress, psychological trauma or chronic psychological stress, reduced immune function, immunosenescence, or macular degeneration.

5. The method of claim 1 , wherein the cell is a somatic cell of endodermal, mesodermal, or ectodermal lineage, or a germ line or embryonic cell.

6. The method of claim 1 , wherein the cell is an induced pluripotent stem cell or a cell used to produce an induced pluripotent stem cell.

7. The method of claim 1 , wherein the cell is a transdifferentiated cell or a cell used to produce a transdifferentiated cell.

8. The method of claim 1 , wherein the cell is an isolated cell, and the administering step lasts no longer than 48 hours.

9. The method of claim 1 , wherein the cell is an isolated cell, and the administering step lasts at least 2 hours.

10. The method of claim 1 , wherein the cell is an isolated cell, and the administering step is performed no more than four times.

11. The method of claim 1 , wherein the cell is an isolated cell, and the administering step is performed at least two times.

12. The method of claim 1 , wherein the cell is an isolated cell, and the method further comprises the step of measuring telomerase activity in the cell.

13. The method of claim 1 , wherein the administering step increases telomerase activity in the cell.

14. The method of claim 13 , wherein the telomerase activity is transiently increased by at least 5%.

15. The method of claim 13 , wherein the half-life of increased telomerase activity is no longer than 48 hours.

16. The method of claim 13 , wherein the half-life of increased telomerase activity is at least 2 hours.

17. The method of claim 1 , wherein the method further comprises the step of measuring telomere length in the cell.

18. The method of claim 1 , wherein the administering step increases average telomere length in the cell.

19. The method of claim 18 , wherein average telomere length in the cell is increased by at least 0.1 kb.

20. The method of claim 1 , wherein the cell is an isolated cell, and the method further comprises the step of measuring population doubling capacity in the cell.

21. The method of claim 1 , wherein the administering step increases population doubling capacity in the cell.

22. The method of claim 21 , wherein the population doubling capacity increases by at least one population doubling.

23. The method of claim 1 , wherein the cell is from or in a mammalian subject.

24. The method of claim 23 , wherein the cell is from or in a human subject.

25. The method of claim 1 , wherein the cell is an isolated cell.

26. The method of claim 1 , wherein the administering step comprises electroporation.

27. The method of claim 1 , wherein the at least one telomere is transiently extended within the cell.

28. The method of claim 1 , wherein the compound is not administered continuously.

29. The method of claim 1 , wherein said isolated cell is part of a cell culture, an isolated tissue culture or an isolated organ.

Assignees

• Univ Leland Stanford Junior

Inventors

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

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title