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.
Warren
Luigi
L
Immune Disease Institute, Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, MA 02115, USA.
Manos
Philip D
PD
Ahfeldt
Tim
T
Loh
Yuin-Han
YH
Li
Hu
H
Lau
Frank
F
Ebina
Wataru
W
Mandal
Pankaj K
PK
Smith
Zachary D
ZD
Meissner
Alexander
A
Daley
George Q
GQ
Brack
Andrew S
AS
Collins
James J
JJ
Cowan
Chad
C
Schlaeger
Thorsten M
TM
Rossi
Derrick J
DJ
D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects*; D012333:RNA, Messenger / Q000494:pharmacology
D012333:RNA, Messenger