Methods for reprogramming somatic cells

• US 8,932,856 B2
• Filed: 10/05/2012
• Issued: 01/13/2015
• Est. Priority Date: 11/26/2003
• Status: Active Grant

• Current Assignee: Whitehead Institute for Biomedical Research
• Original Assignee: Whitehead Institute for Biomedical Research
• Inventors: Jaenisch, Rudolf, Hochedlinger, Konrad
• Primary Examiner(s): Noble, Marcia S
• Application Number:
  US13/646,444
• Publication Number:
  US 20130102080A1
• Time in Patent Office: 830 Days
• Field of Search: 435/377, 435/325
• US Class Current: 435/377
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 67/0273 Cloned vertebrates
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 15/8775 Murine embryos
• CPC Class Codes: C12N 2501/602 Sox-2
• CPC Class Codes: C12N 2501/603 Oct-3/4
• CPC Class Codes: C12N 2501/605 Nanog
• CPC Class Codes: C12N 2506/1307 from adult fibroblasts
• CPC Class Codes: C12N 2510/00 Genetically modified cells
• CPC Class Codes: C12N 2830/003 tet inducible
• CPC Class Codes: C12N 2830/006 tet repressible
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS

Abstract

The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Claims

1. A method of making a somatic cell more susceptible to reprogramming to a pluripotent state comprising introducing at least one exogenous nucleic acid encoding Oct 4 operably linked to at least one regulatory sequence into the cell, thereby increasing expression of Oct4 protein in the somatic cell, wherein increased expression of Oct4 protein makes the cell more susceptible to reprogramming to a pluripotent state.

2. The method of claim 1, further comprising introducing an exogenous nucleic acid encoding Nanog or Sox2 operably linked to at least one regulatory sequence.

3. The method of claim 1, further comprising introducing an exogenous nucleic acid encoding Nanog operably linked to at least one regulatory sequence.

4. The method of claim 1, wherein the somatic cell does not comprise a selectable marker integrated into the endogenous locus of the pluripotency gene.

5. The method of claim 1, wherein the somatic cell is a human cell or a mouse cell.

6. The method of claim 1, wherein the somatic cell is an adult stem cell.

7. The method of claim 6, wherein the adult stem cell is a hematopoietic stem cell, neural stem cell, or mesenchymal stem cell.

8. The method of claim 1, further comprising introducing an endogenous nucleic acid encoding Sox2 operably linked to at least one regulatory sequence.