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Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.

Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.

Pubmed ID: 20888316


  • Warren L
  • Manos PD
  • Ahfeldt T
  • Loh YH
  • Li H
  • Lau F
  • Ebina W
  • Mandal PK
  • Smith ZD
  • Meissner A
  • Daley GQ
  • Brack AS
  • Collins JJ
  • Cowan C
  • Schlaeger TM
  • Rossi DJ


Cell stem cell

Publication Data

November 5, 2010

Associated Grants

  • Agency: NIDCR NIH HHS, Id: RL1 DE019021
  • Agency: NIDCR NIH HHS, Id: RL1DE01902
  • Agency: NHLBI NIH HHS, Id: U01 HL100001
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Cellular Reprogramming
  • Humans
  • Induced Pluripotent Stem Cells
  • RNA, Messenger