@article{f8a935d0526c4dbaa1c8c1076e9f3e9d,
title = "Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA",
abstract = "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.",
author = "Luigi Warren and Manos, {Philip D.} and Tim Ahfeldt and Loh, {Yuin Han} and Hu Li and Frank Lau and Wataru Ebina and Mandal, {Pankaj K.} and Smith, {Zachary D.} and Alexander Meissner and Daley, {George Q.} and Brack, {Andrew S.} and Collins, {James J.} and Chad Cowan and Schlaeger, {Thorsten M.} and Rossi, {Derrick J.}",
note = "Funding Information: The authors wish to thank Sun Hur, Victor Li, Laurence Daheron, Odelya Hartung, Alys Peisley, Sutheera Ratanasirintrawoot, Brad Hamilton, Chenmei Luo, Jonathan Kagan, Julie Sahalie, Alejandro De Los Angeles, and Lior Zangi for help, insight, and suggestions. D.J.R., A.M., G.Q.D, A.S.B, C.C., and T.M.S. were supported by grants from the Harvard Stem Cell Institute. Y.-H.L. is supported by the A∗Star Institute of Medical Biology and Singapore stem cell consortium. T.A. was supported by the Roberto and Allison Mignone Fund for Stem Cell Research. J.J.C. is supported by Howard Hughes Medical Institute, SysCODE (Systems-based Consortium for Organ Design & Engineering), and NIH grant # RL1DE019021. D.J.R. recently founded a company, ModeRNA Therapeutics, dedicated to the clinical translation of this technology. G.Q.D. is a member of the scientific advisory boards and holds equity in the following companies: Epizyme, iPierian, Solasia KK, and MPM Capital, LLP. C.C. is on the SAB of Ipierian. L.W. is a consultant for Stemgent. ",
year = "2010",
month = nov,
day = "5",
doi = "10.1016/j.stem.2010.08.012",
language = "English (US)",
volume = "7",
pages = "618--630",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}