Compositions and methods relating to myomaker-induced muscle cell fusion

Patent metadata

Field	Value
Publication number	US-10272137-B2
Application number	US-201414900005-A
Country	US
Kind code	B2
Filing date	Jun 27, 2014
Priority date	Jun 27, 2013
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present disclosure describes the fusogenic activity of the Myomaker protein. This polypeptide, when expressed in non-muscle cells, is able to drive fusion of the cell with a muscle cell, but not with other non-muscle cells. The use of this protein and cell expressing it in the delivery of exogenous genetic material to muscle cells also is described.

First claim

What is claimed is:

1. A method of fusing a mammalian non-muscle cell to a mammalian muscle cell comprising:
(a) providing a mammalian non-muscle cell comprising an exogenous nucleic acid encoding and expressing a Myomaker protein on the cell surface of said mammalian non-muscle cell; and
(b) contacting said mammalian non-muscle cell with a mammalian muscle cell, wherein said mammalian non-muscle cell expressing the Myomaker protein will fuse with said mammalian muscle cell.

2. The method of claim 1 , wherein said mammalian non-muscle cell is a human cell.

3. The method of claim 1 , wherein said mammalian non-muscle cell is a fibroblast, bone marrow cell or blood cell.

4. The method of claim 2 , wherein said human non-muscle cell is a fibroblast, bone marrow cell or blood cell.

5. The method of claim 1 , wherein said mammalian non-muscle cell is wherein said cell is transformed with exogenous nucleic acid encoding said exogenous Myomaker protein.

6. The method of claim 5 , wherein said exogenous nucleic acid is under the control of constitutive promoter.

7. The method of claim 5 , wherein said exogenous nucleic acid is under the control of an inducible promoter.

8. The method of claim 5 , wherein said exogenous nucleic acid is incorporated into a chromosome of said non-muscle cell.

9. The method of claim 5 , wherein said exogenous nucleic acid is carried episomally by said non-muscle cell.

10. The method of claim 1 , wherein said exogenous nucleic acid further encodes a detectable marker.

11. The method of claim 1 , wherein said mammalian non-muscle cell further comprises a nucleic acid encoding and expressing a gene of interest.

12. The method of claim 5 , wherein said mammalian non-muscle cell is stably transformed.

13. The method of claim 5 , wherein said mammalian non-muscle cell is transiently transfected.

14. A method of delivering a gene of interest to a mammalian muscle cell comprising:
(a) providing a mammalian non-muscle cell comprising an exogenous nucleic acid encoding and expressing a Myomaker protein on the cell surface of said mammalian non-muscle cell, and wherein said mammalian non-muscle cell comprises a nucleic acid that encodes and expresses an exogenous gene of interest; and
(b) contacting said mammalian non-muscle cell with a mammalian muscle cell, wherein said mammalian non-muscle cell expressing the Myomaker protein will fuse with said mammalian muscle cell and deliver said gene of interest to said mammalian muscle cell.

15. The method of claim 14 , wherein said mammalian non-muscle cell is a human cell.

16. The method of claim 14 , wherein said mammalian non-muscle cell is a fibroblast, bone marrow cell or blood cell.

17. The method of claim 15 , wherein said human non-muscle cell is a fibroblast, bone marrow cell or blood cell.

18. The method of claim 14 , wherein said mammalian non-muscle cell is transformed with exogenous nucleic acid encoding said exogenous Myomaker protein.

19. The method of claim 18 , wherein said exogenous nucleic acid is under the control of constitutive promoter.

20. The method of claim 18 , wherein said exogenous nucleic acid is under the control of an inducible promoter.

21. The method of claim 18 , wherein said exogenous nucleic acid is incorporated into a chromosome of said non-muscle cell.

22. The method of claim 18 , wherein said exogenous nucleic acid is carried episomally by said non-muscle cell.

23. The method of claim 14 , wherein said exogenous nucleic acid further encodes a detectable marker.

24. The method of claim 18 , wherein said mammalian non-muscle cell is stably transformed.

25. The method of claim 18 , wherein said mammalian non-muscle cell is transiently transfected.

Assignees

• Univ Texas

Inventors

• Olson Eric
• Millay Douglas P

Classifications

• C12N15/02

  Preparation of hybrid cells by fusion of two or more cells, e.g. protoplast fusion {(monoclonal antibodies C07K16/00; apparatus for cell fusion C12M)} · CPC title

• C12N2740/10071

  Demonstrated in vivo effect · CPC title

• A61K38/1719 Primary

  Muscle proteins, e.g. myosin or actin · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K14/4716

  Muscle proteins, e.g. myosin, actin · CPC title