# US 9,517,250 B2 · Methods for generating cardiomyocytes

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- Number: US 9,517,250 B2
- Document ID: US9517250B2
- Status: Granted
- Kind: B2
- Application number: 13/642,391
- Filed: 2011-04-26
- Published: 2013-08-22
- Granted: 2016-12-13
- Earliest claimed: 2010-04-28
- Assignees: The J. David Gladstone Institutes
- Applicants: Deepak Srivastava; Masaki Ieda
- Inventors: Deepak Srivastava; Masaki Ieda
- Web page: https://patentgrep.com/patent/US9517250B2

## CPC

- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61K 35/34: Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes (vascular smooth muscle A61K35/44)
- A61K 38/1709: {from mammals}
- C12N 5/0657: {Cardiomyocytes; Heart cells}
- C12N 15/85: for animal cells
- C12N 2501/60: Transcription factors
- C12N 2506/1307: from adult fibroblasts
- C12N 2510/00: Genetically modified cells
- C12N 2740/13043: viral genome or elements thereof as genetic vector
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure provides method of generating cardiomyocytes from post-natal fibroblasts. The present disclosure further provides cells and compositions for use in generating cardiomyocytes.

## Claims

### Claim 1

An in vitro method of generating an induced cardiomyocyte, the method consisting of:
genetically modifying a rodent post-natal fibroblast with one or more nucleic acids encoding only three reprogramming factor polypeptides, wherein the three reprogramming factor polypeptides consist of Gata4, Mef2c, and Tbx5, and wherein said genetic modification results in direct reprogramming of the rodent post-natal fibroblast into a cardiomyocyte, thereby generating an induced cardiomyocyte.

### Claim 2 (depends on 1)

The method of claim 1, wherein the post-natal fibroblast is a mouse cell or a rat cell.

### Claim 3 (depends on 1)

The method of claim 1, wherein the three reprogramming factor polypeptides are encoded on a single nucleic acid.

### Claim 4 (depends on 1)

The method of claim 1, wherein said one or more nucleic acids is a recombinant vector.

### Claim 5 (depends on 1)

The method of claim 1, wherein said one or more nucleic acids are operably linked to a transcription regulatory element.

### Claim 6 (depends on 5)

The method of claim 5, wherein the transcription regulatory element is a constitutive promoter functional in the post-natal fibroblast.

### Claim 7

An in vitro method of generating an induced cardiomyocyte, the method consisting of:
genetically modifying a rodent post-natal fibroblast with one or more nucleic acids encoding only three reprogramming factor polypeptides, wherein the three reprogramming factor polypeptides consist of Gata4, Mef2c, and Tbx5, and wherein said genetic modification results in direct reprogramming of the rodent post-natal fibroblast into a cardiomyocyte, thereby generating an induced cardiomyocyte; and
isolating the induced cardiomyocyte.

### Claim 8 (depends on 7)

A method for performing cell transplantation in a rodent recipient, the method comprising:
(i) generating an induced cardiomyocyte from a post-natal fibroblast of a rodent donor according to the method of claim 7; and
(ii) transplanting the induced cardiomyocyte into a rodent recipient that is immunocompatible with the donor.

### Claim 9 (depends on 8)

The method of claim 8, wherein said recipient and said donor are the same individual.

### Claim 10 (depends on 8)

The method of claim 8, wherein said recipient and said donor are different individuals.