The Year in CRISPRs - 16

The Year in CRISPRs * Using CRISPR as a High-Throughput Cancer Screening and Modeling Tool

Ernesto del Aguila III, NHGRI

The research team developed a list
of up to eighteen genes with known or
unknown evidence for their importance
in two forms of liver cancer. They then
introduced the CRISPR-Cas9 molecules,
targeting various combinations of these
genes into mice, which subsequently
developed liver or bile duct cancer
within a few months.

Using CRISPR-Cas9, scientists created a new high-throughput
screening tool for studying the development and progression of
liver cancer in mice.

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| GENengnews.com

"Our approach enables us to
simultaneously target multiple putative
genes in individual cells," noted
co-author Roland Rad, Ph.D., project
leader at the Technical University of
Munich and the German Cancer
Research Center Heidelberg. "We can
now rapidly and efficiently screen which
genes are cancer-causing and which
ones are not. And, we can study how
genes work together to cause cancers-
a crucial piece of the puzzle we must
solve to understand and tackle the
disease."

The investigators were able to
confirm that a set of DNA-binding
proteins called ARID (AT-rich interactive
domain), influence the organization of
chromosomes and are important for
liver cancer development. Furthermore,
mutations in a second protein, TET2,
were found to be causative in bile duct
cancer: although TET2 has not been
found to be mutated in human biliary
cancers, the proteins that it interacts
with have been, showing that the
CRISPR-Cas9 method can identify
human cancer genes that are not
mutated, but whose function is
disturbed by other events.
"The new tools of targeting genes
in combination and inducing insertions
or deletions in chromosomes change our
ability to identify new cancer-causing
genes and to understand their role in
cancer," stated senior group leader
and co-author Allan Bradley, Ph.D.,
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The Year in CRISPRs

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