Compositions for identifying reprogramming factors

• US 8,951,797 B2
• Filed: 10/05/2012
• Issued: 02/10/2015
• 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:
  US13/646,411
• Publication Number:
  US 20130109089A1
• Time in Patent Office: 858 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 composition comprising an isolated primary somatic cell that comprises an exogenously introduced nucleic acid encoding Oct 4, wherein the exogenously introduced nucleic acid increases Oct4 expression in the cell.

2. The composition of claim 1, wherein the isolated primary somatic cell is a mammalian cell.

3. The composition of claim 1, wherein the isolated primary somatic cell is a human cell or a mouse cell.

4. The composition of claim 1, wherein the isolated primary somatic cell is an adult stem cell.

5. The composition of claim 4, wherein the adult stem cell is selected from the group consisting of:

a hematopoietic stem cell, a neural stem cell, and a mesenchymal stem cell.

6. The composition of claim 1, further comprising a candidate agent of interest with respect to its potential to reprogram a somatic cell.

7. The composition of claim 6, wherein the candidate agent of interest is a DNA methylation inhibitor, a histone deacetylase inhibitor or PD098059.

8. The composition of claim 6, wherein the candidate agent of interest is an exogenous nucleic acid encoding a pluripotency protein selected from the group consisting of:

Nanog and Sox-2.

9. A composition comprising a cDNA encoding an Oct4 protein and a cDNA encoding a Sox2 protein, wherein the composition further comprises a DNA methylation inhibitor, a histone deacetylase inhibitor or PD098059.

10. The composition of claim 9, further comprising a cDNA encoding an Oct4 protein and an isolated nucleic acid encoding a Nanog protein.