Highly efficient Cas9-mediated transcriptional programming.

Autor: Chavez A; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Scheiman J; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Vora S; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Pruitt BW; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA., Tuttle M; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA., P R Iyer E; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Lin S; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA. [3] School of Life Sciences, Tsinghua University, Beijing, China., Kiani S; 1] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Guzman CD; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA., Wiegand DJ; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA., Ter-Ovanesyan D; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Braff JL; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA., Davidsohn N; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Housden BE; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA., Perrimon N; 1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA., Weiss R; 1] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Aach J; Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA., Collins JJ; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Institute for Medical Engineering &Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Church GM; 1] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts, USA. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Nature methods [Nat Methods] 2015 Apr; Vol. 12 (4), pp. 326-8. Date of Electronic Publication: 2015 Mar 02.
DOI: 10.1038/nmeth.3312
Abstrakt: The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).
Databáze: MEDLINE