[Catalyst 2017]

CRISPR:
A TIMELINE OF CRISPR:
The phrase “genetic
engineering,” mired in
science fiction and intrigue,
often brings to mind a mad
scientist manipulating mutant genes
or a Frankenstein-like creation
emerging from a test tube. Brought
to light by heated debates over
genetically modified crops, genetic
engineering has long been viewed
as a difficult, risky process fraught
with errors. 1
With the 2012 discovery of CRISPRs,
short for clustered regularly
interspaced sport palindromic
repeats, by Jennifer Doudna of
Berkeley, the world of genetic
engineering has been turned on
its head. 2 Praised as the “Model T”
of genetic engineering, CRISPR is
transforming what it means to edit
genes and in turn, raising difficult
ethical and moral questions along
with it. 3
CRISPR itself is no new discovery.
The repeats are sequences used
by bacteria and microorganisms
to protect against viral infections.
Upon invasion by a virus, CRISPR
identifies the DNA segments from
the invading virus, processes them
into “spacers,” or short segments
of DNA, and inserts them back
into the bacterial genome. 4 When
the bacterial DNA undergoes
transcription, the resulting RNA is a
single-chain molecule that acts as a
guide to destroy viral material. In a
way, the RNA functions as a blacklist
for the bacteria cell: re-invasion
attempts by the same virus are
quickly identified using the DNA
record and subsequently destroyed.
That same blacklist enables CRISPR
to be a powerful engineering tool.
The spacers act as easily identifiable
flags in the genome, allowing
for extremely accurate precision
when manipulating individual
nucleotide sequences in genes. 5
The old biotechnology system can
be perceived as a confused traveler
holding an inaccurate, with a
general location and vague person
to meet. By the same analogy,
CRISPR provides a mugshot of the
person to meet and the precise
coordinates of where to find them.
Scientists have taken advantage of
this precision and now use modified
proteins, often Cas-9, to activate
gene expression as opposed to
PRAISED AS THE
“MODEL T” OF GENETIC
ENGINEERING, CRISPR
IS TRANSFORMING
WHAT IT MEANS TO
EDIT GENES.
cutting the DNA, an innovative style
of genetic engineering. 6 Traditional
genetic engineering can be a shot
in the dark- however, with the
accuracy of CRISPR, mutations
are very rare. 7 For the first time,
scientists are able to pinpoint the
exact destination of genes, cut the
exact desired sequence, and leave
no damage. Another benefit of
CRISPR is the reincorporation of
genes that have become lost, either
by breeding or evolution, bringing
back extinct qualities: such as
mammoth genes in living elephant
cells. 8,9 Even better, CRISPR is very
inexpensive - around $75 to edit a
gene at Baylor College of Medicine
- and accessible to anyone with
biological expertise, starting with
graduate students. 11 Thus, the term
“Model T of genetic engineering”
could hardly be more appropriate.
CRISPR stretches the boundaries of
bioengineering. One enterprising
team from China led by oncologist
Dr. Lu You has already begun trials
on humans. They plan on injecting
cells modified with CRISPR-Cas9
system into patients with metastatic
non-small cell lung cancer: patients
who otherwise have little hope of
survival. 12 Extracted T cells, critical
immune cells, will be edited with
the CRISPR-Cas9 system to identify
and “snip” out a gene that encodes
PD-1, a protein that acts as a check
on the cell’s capacity to launch
an immune response, to prevent
attacks on healthy cells. Essentially,
Lu’s team is creating super-T-cells:
ones that have no mercy for any
suspicious activity. This operation
is very risky: for one, CRISPR’s
mechanisms are not thoroughly
understood, and mistakes with
1987
Short direct
repeats found in
E.coli
2002
“CRISPR” coined
by Jansen et
al to describe
repeats
2005
Spacer
sequences
found to be
viral in nature
2007
First evidence
of CRISPR-Cas
partnership
2008
DNA found to
be the target
of CRISPR-Cas
systems
2010
CRISPR-Cas
systems are
found to be able
to cut DNA
18 | CATALYST