You’ve probably heard of CRISPR technologies
and their much-discussed ability to edit our
DNA.
For the most part, these stories probably
refer to CRISPR-Cas9.
But a new system, CRISPR-Cas3, has just been
used in human cells for the very first time...and
offers a whole new set of tools that could
have huge implications for curing previously
incurable viruses.
To review, CRISPR-Cas9 is the combination
of a custom-made piece of RNA (that’s the
clustered regularly interspersed palindromic
repeats, or the CRISPR part) and an enzyme
(that’s the CRISPR associated protein 9,
or Cas-9 part).
The RNA is engineered to recognize a certain
segment of DNA, which guides the CRISPR-Cas9
system to that section so it can then cut
and delete, or potentially add to, or even
replace with an altered version.
CRISPR-Cas9 belongs to a family of CRISPR-based
editing tools called Class 2 systems.
There are actually three classes of CRISPR-Cas
systems, most of them belonging to classes
one and two.
CRISPR-Cas3 is a Class 1 system.
Class 1 systems are apparently more prevalent
in our biological processes and are more sophisticated
than Class 2 systems, but have so far they’ve
only been used experimentally as gene editing
tools in bacteria and archaea.
CRISPR-Cas3 has the unique capability to search
for, identify, and delete much longer stretches
of DNA than CRISPR-Cas9, chunks up to 100,000
base pairs long—and it makes multiple cuts
along that chunk, kind of like a shredder.
A research team that recently demonstrated
this in human cells for the first time--in
a petri dish--believes the Cas3 system could
be a better option than Cas9 because it uses
a longer guide RNA sequence.
This means it’s better at more accurately
locating the chunk we want to target.
This makes it ideal for editing non-coding
segments of our genome.
These are pieces of our DNA, about 98% of
it, actually, that don’t directly correlate
to something.
Instead they act as regulators, determining
how much that gene is expressed, if at all.
We don’t have a great understanding of what
this huge swathe of our DNA really does, so
using CRISPR-Cas3 to delete large sections
and then seeing what happens, in a lab setting
of course, could give us a much better understanding
of what these non-coding sections do and how
they work.
CRISPR-Cas3 could also delete sections of
genes that have been permanently altered by
viruses.
Diseases like herpes actually hijack our DNA,
inserting their sequences into our genome
to use our cell’s machinery to make their
own often malicious proteins.
Herpes in particular is spectacularly good
at avoiding our immune system and goes through
dormant stages, making it impossible to cure.
But its permanent alterations of our DNA could
make it vulnerable to attack by CRISPR technologies,
and CRISPR-Cas3’s accurate targeting and
powerful shredding capabilities could knock
it out of our system for good.
Some other teams are pointing to CRISPR-Cas3
as a potential solution for antibiotic-resistant
bacteria.
Instead of deleting a sequence of DNA infected
by a virus’ DNA, CRISPR-Cas3 could just
chew up the bacterium’s whole genome beyond
the point of repair, causing the organism’s
death—no antibiotics required!
So, CRISPR-Cas3 has the potential to delete
large chunks of our DNA, proving useful and
potentially more efficient and cost-effective
in some essential medical situations—but
we still have to learn how to control it.
While the most recent study into CRISPR-Cas3’s
potential did demonstrate that we can use
it in human cells, we still don’t have total
control over how long a section we tell it
to delete.
And of course, since we’re not even entirely
sure of the complete function of most of our
genes, we would want to make sure the stuff
we’re deleting is, y’know...safe to delete.
Or that we have a healthy version to replace
it with, some kind of backup plan.
There are all kinds of new studies coming
out about the unexpected effects of CRISPR-Cas9—
deletions we didn’t mean to make and didn’t
see coming—so with all of this gene-editing
stuff we’ll need to proceed with extreme
caution and many more years of experimentation
before we see this in a clinical setting.
But this new exploration of CRISPR-Cas3’s
potential is an exciting first proof-of-concept
for a technology that could one day provide
a solution for previously incurable viruses.
If you want to learn more about viruses, you
should check out our new show, Sick.
It's all about what's happening in your body
when things start to go wrong.
We're talking Lyme disease, measles, lupus,
and more.
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to cover?
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