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A split-Cas9 architecture for inducible genome editing and transcription modulation

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Figure 1: Generation and optimization of inducible split-Cas9 fragments.
Figure 2: Inducible transcriptional activation using split dCas9-VP64 fusions.


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We would like to thank N.E. Sanjana, S. Konermann, M.D. Brigham, A. Trevino, F.A. Ran and W. Yan for technical assistance, S. Jones, M. Heidenreich and K. Zheng for editing and members of the Zhang laboratory for discussion, support and advice. F.Z. is supported by the National Institute of Mental Health (NIMH) through a National Institutes of Health (NIH) Director's Pioneer Award (DP1-MH100706), the National Institute of Neurological Disorders and Stroke (NINDS) through an NIH Transformative R01 grant (R01-NS 07312401), National Science Foundation (NSF) Waterman Award, the Keck, Damon Runyon, Searle Scholars, Klingenstein, Vallee, Merkin and Simons Foundations, and Bob Metcalfe, New York Stem Cell Foundation. F.Z. is a New York Stem Cell Foundation Robertson Investigator. CRISPR reagents are available to the academic community through Addgene, and associated protocols, support forum and computational tools are available via the Zhang laboratory website (

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Authors and Affiliations



B.Z. and F.Z. conceived the project and designed the experiments. B.Z. and S.E.V. performed experiments and analyzed data. B.Z. and F.Z. wrote the paper with help from all authors.

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Correspondence to Feng Zhang.

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Competing interests

Feng Zhang is a scientific advisor of Editas Medicine and of Horizon Discovery.

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Supplementary Figures 1 and 2, Supplementary Tables 1–5, Supplementary Methods (PDF 1641 kb)

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Zetsche, B., Volz, S. & Zhang, F. A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat Biotechnol 33, 139–142 (2015).

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