What Happens When CRISPR Backfires?

With all the hubbub about CRISPR in the news,
it may feel like using it to pick your kids eye-color is just around the corner. But this seemingly miraculous gene-editing
technology may not actually be as simple–or as safe–as we thought. Just so we’re all on the same page, CRISPR
(or more accurately CRISPR-cas9) works by cutting the DNA of a cell at a designated
spot, say a section of DNA that represents a certain gene. Then, when the cell tries to repair the damaged
DNA, it often ends up just disabling the gene altogether. This has all kinds of uses. Maybe we want to turn off a gene that produces
too much of a certain protein? CRISPR can do that. Say we want to see what a certain gene even
does? CRISPR can help us do that too. Ever since it was first used to edit living
cells in 2013, CRISPR has been touted as a promising technology for treating inherited
disorders, cancer, and other diseases with no current treatment options. Teams of researchers around the globe had
even hoped to begin human trials in 2018. But none of those trials have taken place
yet, with the exception of China, where researchers have been working with CRISPR in humans since
2016–no results from these trials have been published so far. And in the US, the FDA just placed a ‘clinical
hold’ on the first proposed CRISPR gene editing human trial. But why? Several new studies released in the last few
months suggest we need to be more cautious when editing the human genome. Two of these studies found that when CRISPR
performs its hallmark trick and cuts DNA, that damage can kill the cell, or make it
stop growing. CRISPR modifications are also less likely
to kill cells that have a defective version of a gene called p53. P53 plays a role in preventing the onset of
cancer by regulating a cell’s life cycle, so by leaving more of the defective cells
alive than healthy ones*, CRISPR may be inadvertently raising the risk of cancer in that patient. Which is, like, the opposite of the goal. And we haven’t even gotten to the most recent
study that raises concerns. Up until now, CRISPR-cas9’s cutting function
has been accurate in the specific area of interest–the spot in the DNA that’s supposed
to be cut. But that’s because researchers were only
looking for mutations caused by CRISPR in the immediate vicinity of the cut. New research reveals that in about 20% of
cells, CRISPR results in MUCH larger deletions than we thought**– up to more than 100 base
pairs. Researchers didn’t notice this before because
they were looking for harmful mutations and didn’t see any…but that’s because the
entire region was gone. In CRISPR treatments that would target billions
of cells inside the human body, this could lead to, again…a risk of cancer. Putting us right back at square one. So the human trials have been delayed…where
do we go from here? CRISPR permanently alters your genome, so
we want to make sure we get it right before we make moves in real human bodies. Well, science marches on. New and improved versions of this kind of
technology are already racing forward, like a genetic editing tool called REPAIR, which
uses a different cutting enzyme–Cas13. REPAIR works with RNA, instead of DNA, to
make temporary or reversible changes. There’s also a newly engineered protein
that can alter individual base pairs rather than a whole chunk of DNA, acting more like
surgical forceps than a pair of kitchen scissors. So continued progress and exciting breakthroughs
in this field are still happening–we’re not at the end of our CRISPR rope yet. It’s just that we need to take a step back
from the hype and carefully analyze what’s really going to be safe as we move forward. To stay current with all the CRISPR news that’s
sure to be plentiful in the coming years, subscribe to Seeker, and for more on how your
body, specifically your immune system, interacts with the technology, check out this video
from Julian. And, fun fact, CRISPR doesn’t just present
possibilities in human biology–it could be used to produce genetically crops too. I’m Maren, thanks for watching Seeker.


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