The Year in CRISPRs - 18

CRISPR Triple Checks
Its Target before Cutting
F

rom the co-discoverer of the CRISPR-Cas9
system and her colleagues at UC Berkeley
comes new data that should instill a greater level
of confidence that the genome editing tool won't
inadvertently excise off-target DNA.
The two new reports from the Berkeley
investigators show in great detail how the Cas9
protein searches through billions of base pairs in
a cell to find the right DNA sequence, and how
Cas9 determines whether to bind or bind and
cut, thereby initiating gene editing. From the
collected data, the researchers were able to

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| GENengnews.com

surmise that Cas9 appears to have at least three
ways of checking to make sure it finds the right
target DNA before it takes the irrevocable step
of making a cut.
"CRISPR-Cas9 has evolved for accurate
DNA targeting, and we now understand the
molecular basis for its seek-and-cleave activity,
which helps limit off-target DNA editing,"
explained senior author of both articles and
co-discover of the CRISPR-Cas9 system Jennifer
Doudna, Ph.D., a Howard Hughes Medical
Institute investigator and professor of molecular

and cell biology and of chemistry at UC Berkeley.
The findings from this study were
published in November in two papers: the
first in Science through an article entitled
"Dynamics of CRISPR-Cas9 genome interrogation
in living cells" and the second in Nature in an
article titled "Conformational control of DNA
target cleavage by CRISPR-Cas9."
In the Science article, the researchers
tracked Cas9-RNA molecules within the nucleus
of mammalian cells as they rapidly searched
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The Year in CRISPRs

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