Journal
NATURE METHODS
Volume 12, Issue 4, Pages 326-U65Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.3312
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Funding
- US Department of Energy [DE-FG02-02ER63445]
- Wyss Institute for Biologically Inspired Engineering
- National Cancer Institute [5T32CA009216-34]
- National Science Foundation Graduate Research Fellowship Program
- Department of Biological Engineering at the Massachusetts Institute of Technology
- Department of Genetics at Harvard Medical School
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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).
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