cancer genomics
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CRISPR cancer therapy doesn’t kill healthy cells A new cancer therapy called CINDELA, developed by researchers from South Korea’s Institute for Basic Science (IBS), employs CRISPR-Cas9 to kill cancer cells without affecting normal tissues. The breakthrough has been published in the journal PNAS.
R
First, the researchers confirmed that
mice. It was found that the CINDELA treatment
enzyme-driven DNA double-strand breaks using
can substantially suppress the growth of tumours in
CRISPR were able to induce cell deaths in cancer
these mice. Notably, since CINDELA targets InDel
similar to physical or chemical breaks driven
mutations which are generated as by-products
adiation and chemotherapy destroy
by radiation or chemotherapies, respectively.
during tumorigenesis, CINDELA can be applied
cancer cells by producing DNA double-strand breaks.
Then, they performed bioinformatics analysis
to treat most tumours.
Unfortunately, since both treatments target DNA in
to identify unique InDel mutations in several
“We believe CINDELA can become a novel
normal cells as well as cancer cells, indiscriminate
different cancer cell lines, including breast,
therapeutic application for cancer treatments as
killing of healthy cells and side effects are unavoidable
colon, leukaemia and glioblastoma, which are not
personalised and precision medicine for all cancer
when using these treatments. Scientists have long been
found in normal cells. Based on this information,
patients without severe side effects,” said CGI
searching for a method to selectively target only cancer
they successfully made CRISPR-Cas9 reagents
Director Kyungjae Myung. The researchers have
cells without affecting normal cells; now, researchers
targeting those mutations.
already started applying this technology in tumours
at the IBS Center for Genomic Integrity (CGI) have
The scientists named this new treatment
directly taken from patients, with research groups
combined the concepts of cancer genomics and
CINDELA, which stands for ‘cancer-specific
having expertise in the relevant technologies, such
CRISPR-Cas9 (commonly called genetic scissors)
InDel attacker’, and confirmed that it was able
as gene delivery, companion diagnostic platform
to propose a potential solution.
to selectively kill cancer cells without affecting
and cancer genomics.
Cancer genomics projects have found that
normal cells. It was discovered that CINDELA-
One obstacle that the researchers had during
regardless of their origins, most cancer cells
driven cancer cell death was dependent on the
all these experiments was the delivery of CINDELA
accumulate many mutations including small
number of DNA double-strand breaks created by
reagents to tumours. Although the researchers
insertion/deletion (InDel) of several nucleotides,
CRISPR-Cas9; for example, a CINDELA reagent
could achieve significant tumour growth inhibition
single nucleotide changes and large chromosomal
which induced 50 breaks in the DNA was much
using a high titre of the virus to deliver the CRISPR
aberrations. Meanwhile, CRISPR-Cas9 can be used
better at killing cancer cells than the reagent that
in mice, as of yet this may not be enough to directly
to make DNA double-strand breaks in a sequence-
induced only 10 breaks.
treat human patients. However, such an obstacle
specific manner. The CGI researchers proposed
In addition to cancer cell line experiments, the
is one of the major issues in the current CRISPR-
that by using CRISPR-Cas9 to produce DNA
researchers conducted further animal studies to
Cas9 field. Researchers believe that in the near
double-strand breaks at cancer-specific mutations
verify CINDELA’s efficacy in living organisms. To
future, the development of new delivery systems
that only exist in cancer cells, they could trigger cell
do so, tumour cells (colon and lung cancer) were
will eventually help establish the CINDELA cancer
death in cancer cells without affecting normal cells.
derived from patients and were xenografted into
treatment technology in cancer patients.
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