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Cas9-triggered chain ablation of cas9 as a gene drive brake

Nature Biotechnology volume 34, pages 137–138 (2016)Cite this article

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With the advent of clustered, regularly interspaced, short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) technology1,2, researchers can construct gene drives that can bias the inheritance of edited alleles to alter entire populations3,4. As demonstrated with the mutagenic chain reaction in Drosophila4, the CRISPR-Cas9 system can propagate genomic modification together with the genome-editing machinery itself. Although gene drives might have the potential to control insect-borne diseases and agricultural pests5, substantial concerns have been raised over unanticipated ecological consequences as a result of drive use6. Here we report the development of a potential Cas9-based gene drive 'brake' that remains inert in a wild-type genome but is activated by Cas9 to both cleave the genomic cas9 sequence and to convert an incoming cas9 allele into a brake. This means that the propagation of the brake is favored in a cas9-carrying population.

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Figure 1: Schematics and proof of principle of CATCHA.

References

  1. Hsu, P.D., Lander, E.S. & Zhang, F. Cell 157, 1262–1278 (2014).

    Article  CAS  Google Scholar 

  2. Doudna, J.A. & Charpentier, E. Science 346, 1258096 (2014).

    Article  Google Scholar 

  3. DiCarlo, J.E. et al. bioRxiv (2015). doi:10.1101/013896

  4. Gantz, V.M. & Bier, E. Science 348, 442–444 (2015).

    Article  CAS  Google Scholar 

  5. Esvelt, K.M., Smidler, A.L., Catteruccia, F. & Church, G.M. Elife doi:10.7554/eLife.03401 (17 July 2014).

  6. Akbari, O.S. et al. Science 349, 927–929 (2015).

    Article  CAS  Google Scholar 

  7. Gratz, S.J. et al. Genetics 196, 961–971 (2014).

    Article  CAS  Google Scholar 

  8. Hay, B., Jan, L.Y. & Jan, Y.N. Cell 55, 577–587 (1988).

    Article  CAS  Google Scholar 

  9. Lasko, P.F. & Ashburner, M. Genes Dev. 4, 905–921 (1990).

    Article  CAS  Google Scholar 

  10. Port, F., Chin, H.-M., Lee, T. & Bullock, S.L. Proc. Natl. Acad. Sci. USA 111, E2967–E2976 (2014).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank D. Luginbuhl for generating transgenic flies, F. Port for providing gRNA flies, and J. Luo, T. Mosca, X. Wang, J. Li and J. Lui for advice and critical comments. This study was supported by an NIH grant (R01-DC005982) to L.L. X.J.G. was supported by an Enlight Foundation Interdisciplinary Fellowship. L.L. is an HHMI investigator.

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  1. Xiaojing J Gao

    Present address: Present address: Division of Biology, California Institute of Technology, Pasadena, California, USA.,

  2. Bing Wu and Xiaojing J Gao: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, California, USA

    Bing Wu, Liqun Luo & Xiaojing J Gao

Authors
  1. Bing Wu
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  2. Liqun Luo
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Correspondence to Liqun Luo.

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Wu, B., Luo, L. & Gao, X. Cas9-triggered chain ablation of cas9 as a gene drive brake. Nat Biotechnol 34, 137–138 (2016). https://doi.org/10.1038/nbt.3444

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