PerspectiveMolecular Biology

CRISPR at lightning speeds

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Science  12 Jun 2020:
Vol. 368, Issue 6496, pp. 1180-1181
DOI: 10.1126/science.abc3997

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Summary

Fundamental studies since the mid-1990s demonstrated the power of targeting DNA double-strand breaks (DSBs). This work uncovered a plethora of DNA repair pathways and formed the basis for the revolution in genome modification (1). That revolution in its most powerful manifestation came about with the discovery of RNA-directed DNA-cleaving enzymes in CRISPR systems, allowing the simple rules of base-pairing to guide targeted DNA breakage. Yet the CRISPR-associated 9 (Cas9) endonuclease that induces a DSB at target sites (determined by guide RNAs) in gene editing has been delivered as a relatively blunt instrument, with little control over its activity. On page 1265 of this issue, Liu et al. (2) developed Cas9 into a precision instrument that is both temporally and spatially controlled. It should now be possible to interrogate the cellular response to DSBs in real time, which will allow greater understanding of how cells maintain genome integrity when faced with these potentially catastrophic lesions.

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