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A CRISPR/Cas9-based system for reprogramming cell lineage specification.


ABSTRACT: Gene activation by the CRISPR/Cas9 system has the potential to enable new approaches to science and medicine, but the technology must be enhanced to robustly control cell behavior. We show that the fusion of two transactivation domains to Cas9 dramatically enhances gene activation to a level that is necessary to reprogram cell phenotype. Targeted activation of the endogenous Myod1 gene locus with this system led to stable and sustained reprogramming of mouse embryonic fibroblasts into skeletal myocytes. The levels of myogenic marker expression obtained by the activation of endogenous Myod1 gene were comparable to that achieved by overexpression of lentivirally delivered MYOD1 transcription factor.

SUBMITTER: Chakraborty S 

PROVIDER: S-EPMC4264059 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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A CRISPR/Cas9-based system for reprogramming cell lineage specification.

Chakraborty Syandan S   Ji HaYeun H   Kabadi Ami M AM   Gersbach Charles A CA   Christoforou Nicolas N   Leong Kam W KW  

Stem cell reports 20141023 6


Gene activation by the CRISPR/Cas9 system has the potential to enable new approaches to science and medicine, but the technology must be enhanced to robustly control cell behavior. We show that the fusion of two transactivation domains to Cas9 dramatically enhances gene activation to a level that is necessary to reprogram cell phenotype. Targeted activation of the endogenous Myod1 gene locus with this system led to stable and sustained reprogramming of mouse embryonic fibroblasts into skeletal m  ...[more]

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