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.
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