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A light-inducible CRISPR-Cas9 system for control of endogenous gene activation


Optogenetic systems enable precise spatial and temporal control of cell behavior. We engineered a light-activated CRISPR-Cas9 effector (LACE) system that induces transcription of endogenous genes in the presence of blue light. This was accomplished by fusing the light-inducible heterodimerizing proteins CRY2 and CIB1 to a transactivation domain and the catalytically inactive dCas9, respectively. The versatile LACE system can be easily directed to new DNA sequences for the dynamic regulation of endogenous genes.

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Figure 1: Light-inducible, RNA-guided activation of endogenous human genes by the LACE system.
Figure 2: Dynamic spatial and temporal transcriptional control using the LACE system.


  1. Beerli, R.R., Dreier, B. & Barbas, C.F. III. Proc. Natl. Acad. Sci. USA 97, 1495–1500 (2000).

    CAS  Article  Google Scholar 

  2. Zhang, F. et al. Nat. Biotechnol. 29, 149–153 (2011).

    Article  Google Scholar 

  3. Miller, J.C. et al. Nat. Biotechnol. 29, 143–148 (2011).

    CAS  Article  Google Scholar 

  4. Konermann, S. et al. Nature 500, 472–476 (2013).

    CAS  Article  Google Scholar 

  5. Qi, L.S. et al. Cell 152, 1173–1183 (2013).

    CAS  Article  Google Scholar 

  6. Gilbert, L.A. et al. Cell 154, 442–451 (2013).

    CAS  Article  Google Scholar 

  7. Perez-Pinera, P. et al. Nat. Methods 10, 973–976 (2013).

    CAS  Article  Google Scholar 

  8. Maeder, M.L. et al. Nat. Methods 10, 977–979 (2013).

    CAS  Article  Google Scholar 

  9. Cheng, A.W. et al. Cell Res. 23, 1163–1171 (2013).

    CAS  Article  Google Scholar 

  10. Farzadfard, F., Perli, S.D. & Lu, T.K. ACS Synth. Biol. 2, 604–613 (2013).

    CAS  Article  Google Scholar 

  11. Mali, P. et al. Nat. Biotechnol. 31, 833–838 (2013).

    CAS  Article  Google Scholar 

  12. Kabadi, A.M., Ousterout, D.G., Hilton, I.B. & Gersbach, C.A. Nucleic Acids Res. 42, e147 (2014).

    Article  Google Scholar 

  13. Jinek, M. et al. Science 337, 816–821 (2012).

    CAS  Article  Google Scholar 

  14. Shimizu-Sato, S., Huq, E., Tepperman, J.M. & Quail, P.H. Nat. Biotechnol. 20, 1041–1044 (2002).

    CAS  Article  Google Scholar 

  15. Yazawa, M., Sadaghiani, A.M., Hsueh, B. & Dolmetsch, R.E. Nat. Biotechnol. 27, 941–945 (2009).

    CAS  Article  Google Scholar 

  16. Kennedy, M.J. et al. Nat. Methods 7, 973–975 (2010).

    CAS  Article  Google Scholar 

  17. Wang, X., Chen, X. & Yang, Y. Nat. Methods 9, 266–269 (2012).

    CAS  Article  Google Scholar 

  18. Polstein, L.R. & Gersbach, C.A. J. Am. Chem. Soc. 134, 16480–16483 (2012).

    CAS  Article  Google Scholar 

  19. Müller, K. et al. Nucleic Acids Res. 41, e77 (2013).

    Article  Google Scholar 

  20. Motta-Mena, L.B. et al. Nat. Chem. Biol. 10, 196–202 (2014).

    CAS  Article  Google Scholar 

  21. Gautier, A. et al. Nat. Chem. Biol. 10, 533–541 (2014).

    CAS  Article  Google Scholar 

  22. Perez-Pinera, P. et al. Nat. Methods 10, 239–242 (2013).

    CAS  Article  Google Scholar 

  23. Maeder, M.L. et al. Nat. Methods 10, 243–245 (2013).

    CAS  Article  Google Scholar 

  24. Olson, E.J. & Tabor, J.J. Nat. Chem. Biol. 10, 502–511 (2014).

    CAS  Article  Google Scholar 

  25. Chakraborty, S. et al. Stem Cell Reports 3, 940–947 (2014).

    CAS  Article  Google Scholar 

  26. Polstein, L.R. & Gersbach, C.A. Methods Mol. Biol. 1148, 89–107 (2014).

    CAS  Article  Google Scholar 

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C. Tucker (University of Colorado–Denver) provided CRY2 and CIBN plasmids. P. Vosburgh designed and fabricated the three-dimensional photomasks. This work was supported by a US National Institutes of Health (NIH) Director–s New Innovator Award (DP2OD008586), US National Science Foundation Faculty Early Career Development Award (CBET-1151035), NIH R01DA036865, NIH R03AR061042, NIH P30AR066527, and an American Heart Association Scientist Development Grant (10SDG3060033 to C.A.G.). L.R.P. was supported by an American Heart Association Predoctoral Fellowship and NIH Biotechnology Training Grant (T32GM008555).

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L.R.P. and C.A.G. designed experiments, analyzed the data and wrote the manuscript. L.R.P. performed experiments.

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Correspondence to Charles A Gersbach.

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The authors declare no competing financial interests.

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Polstein, L., Gersbach, C. A light-inducible CRISPR-Cas9 system for control of endogenous gene activation. Nat Chem Biol 11, 198–200 (2015).

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