[Catalyst 2017]
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CRISPR:<br />
A TIMELINE OF CRISPR:<br />
The phrase “genetic<br />
engineering,” mired in<br />
science fiction and intrigue,<br />
often brings to mind a mad<br />
scientist manipulating mutant genes<br />
or a Frankenstein-like creation<br />
emerging from a test tube. Brought<br />
to light by heated debates over<br />
genetically modified crops, genetic<br />
engineering has long been viewed<br />
as a difficult, risky process fraught<br />
with errors. 1<br />
With the 2012 discovery of CRISPRs,<br />
short for clustered regularly<br />
interspaced sport palindromic<br />
repeats, by Jennifer Doudna of<br />
Berkeley, the world of genetic<br />
engineering has been turned on<br />
its head. 2 Praised as the “Model T”<br />
of genetic engineering, CRISPR is<br />
transforming what it means to edit<br />
genes and in turn, raising difficult<br />
ethical and moral questions along<br />
with it. 3<br />
CRISPR itself is no new discovery.<br />
The repeats are sequences used<br />
by bacteria and microorganisms<br />
to protect against viral infections.<br />
Upon invasion by a virus, CRISPR<br />
identifies the DNA segments from<br />
the invading virus, processes them<br />
into “spacers,” or short segments<br />
of DNA, and inserts them back<br />
into the bacterial genome. 4 When<br />
the bacterial DNA undergoes<br />
transcription, the resulting RNA is a<br />
single-chain molecule that acts as a<br />
guide to destroy viral material. In a<br />
way, the RNA functions as a blacklist<br />
for the bacteria cell: re-invasion<br />
attempts by the same virus are<br />
quickly identified using the DNA<br />
record and subsequently destroyed.<br />
That same blacklist enables CRISPR<br />
to be a powerful engineering tool.<br />
The spacers act as easily identifiable<br />
flags in the genome, allowing<br />
for extremely accurate precision<br />
when manipulating individual<br />
nucleotide sequences in genes. 5<br />
The old biotechnology system can<br />
be perceived as a confused traveler<br />
holding an inaccurate, with a<br />
general location and vague person<br />
to meet. By the same analogy,<br />
CRISPR provides a mugshot of the<br />
person to meet and the precise<br />
coordinates of where to find them.<br />
Scientists have taken advantage of<br />
this precision and now use modified<br />
proteins, often Cas-9, to activate<br />
gene expression as opposed to<br />
PRAISED AS THE<br />
“MODEL T” OF GENETIC<br />
ENGINEERING, CRISPR<br />
IS TRANSFORMING<br />
WHAT IT MEANS TO<br />
EDIT GENES.<br />
cutting the DNA, an innovative style<br />
of genetic engineering. 6 Traditional<br />
genetic engineering can be a shot<br />
in the dark- however, with the<br />
accuracy of CRISPR, mutations<br />
are very rare. 7 For the first time,<br />
scientists are able to pinpoint the<br />
exact destination of genes, cut the<br />
exact desired sequence, and leave<br />
no damage. Another benefit of<br />
CRISPR is the reincorporation of<br />
genes that have become lost, either<br />
by breeding or evolution, bringing<br />
back extinct qualities: such as<br />
mammoth genes in living elephant<br />
cells. 8,9 Even better, CRISPR is very<br />
inexpensive - around $75 to edit a<br />
gene at Baylor College of Medicine<br />
- and accessible to anyone with<br />
biological expertise, starting with<br />
graduate students. 11 Thus, the term<br />
“Model T of genetic engineering”<br />
could hardly be more appropriate.<br />
CRISPR stretches the boundaries of<br />
bioengineering. One enterprising<br />
team from China led by oncologist<br />
Dr. Lu You has already begun trials<br />
on humans. They plan on injecting<br />
cells modified with CRISPR-Cas9<br />
system into patients with metastatic<br />
non-small cell lung cancer: patients<br />
who otherwise have little hope of<br />
survival. 12 Extracted T cells, critical<br />
immune cells, will be edited with<br />
the CRISPR-Cas9 system to identify<br />
and “snip” out a gene that encodes<br />
PD-1, a protein that acts as a check<br />
on the cell’s capacity to launch<br />
an immune response, to prevent<br />
attacks on healthy cells. Essentially,<br />
Lu’s team is creating super-T-cells:<br />
ones that have no mercy for any<br />
suspicious activity. This operation<br />
is very risky: for one, CRISPR’s<br />
mechanisms are not thoroughly<br />
understood, and mistakes with<br />
1987<br />
Short direct<br />
repeats found in<br />
E.coli<br />
2002<br />
“CRISPR” coined<br />
by Jansen et<br />
al to describe<br />
repeats<br />
2005<br />
Spacer<br />
sequences<br />
found to be<br />
viral in nature<br />
2007<br />
First evidence<br />
of CRISPR-Cas<br />
partnership<br />
2008<br />
DNA found to<br />
be the target<br />
of CRISPR-Cas<br />
systems<br />
2010<br />
CRISPR-Cas<br />
systems are<br />
found to be able<br />
to cut DNA<br />
18 | CATALYST