[♪ INTRO]
One of the biggest scientific developments of this century
has been the gene-editing tool CRISPR.
It’s a technology that makes it possible to find and edit
a specific piece of a cell’s DNA.
This is huge. In fact, the 2020 Nobel Prize in Chemistry
went to the scientists who did breakthrough research in this field.
Now, CRISPR is actually a natural system in bacteria that evolved
to fight invaders like viruses—basically by chopping up their DNA.
But these researchers showed that it was possible to extract and modify
the bacteria’s natural defense system to target and cut DNA in other organisms,
and to specifically program what DNA would be cut.
Which is why CRISPR systems are often described as “molecular scissors.”
But these systems, sometimes just called CRISPR for short,
can do far more than just cut DNA.
Here are four examples of how CRISPR isn’t just molecular scissors:
It’s like a cellular Swiss army knife!
One surprising area where CRISPR shows a lot of promise is in creating antibiotics.
Antibiotics like penicillin have saved millions of lives
from bacterial illnesses like pneumonia and scarlet fever.
They work by killing bacteria, or slowing down their growth.
But the widespread use of antibiotics over the last century
has led to the rise of bacteria that are resistant to antibiotics.
And if even a few bacteria can resist antibiotics,
they can quickly spread and become extremely hard to treat.
Unfortunately, finding or developing new antibiotics is hard, and we’re in a race
against time as more strains of bacteria evolve to resist our traditional ones.
But scientists are now turning to CRISPR
as a potential new way to fight infectious bacteria!
That’s a little counterintuitive, because CRISPR systems actually
evolved in bacteria… as a way to protect them.
The way it worked was, after a bacterium encountered a virus once,
these natural CRISPR systems would store pieces of the viral DNA
in the bacterium’s own genome.
That way, it could quickly identify the virus if it ever showed up again.
If it did, the bacterium would use a special protein
called a Cas protein to chop up that virus’s genome.
So originally, CRISPR was destroying viruses, not bacteria.
But by engineering these natural systems to target other kinds of DNA,
scientists can turn CRISPRCas systems into weapons against bacteria as well.
And that’s exactly what scientists at the University of Wisconsin-Madison are doing.
They’re creating special CRISPR DNA messages
that tell the Cas proteins to cut the bacteria’s own DNA.
Then they package these messages into circles of DNA called plasmids.
Next, they load these plasmids into viruses that infect bacterial cells,
known as bacteriophages. These are exactly the kind of viruses
that CRISPR evolved to fight.
When these engineered bacteriophages infect the target bacteria,
the cell thinks it’s under attack. The enclosed DNA message is released,
and that triggers the bacteria’s own Cas proteins to chop up its own genome.
And that can wipe out the bacteria!
For now, these CRISPR antibiotics are still in the works,
but eventually they could be a way to fight antibiotic-resistant bacteria.
Like, one of the main targets of this new technology is the bacterium C. difficile,
which is resistant to various antibiotics and can be deadly.
It causes diarrhea and colon inflammation,
and makes up to half a million people sick in the U.S. alone each year.
So, if all goes well, in the future,
this technology could prevent countless avoidable illnesses.
These days, we’re all a bit more aware of just how important it is
to quickly, easily, and accurately diagnose an infection.
But if you’ve ever been tested for an infectious disease before, you probably had to
wait a few days for the doctor to send your tests off to the lab to get results.
It would be much more convenient if your doctor could just perform the test
and give you the results right there on the spot.
And that may actually be possible with CRISPR.
The idea is this: It all comes down to special types of Cas proteins
that are especially destructive. Unlike others, which only destroy their target,
when these Cas proteins find their target, they will cut it and anything nearby!
This is called collateral cleavage.
So, in practice, the target would be a tiny piece of the disease you’re testing for.
Like maybe a small piece of the SARS-CoV-2 genome,
which is the virus that causes COVID.
Your doctor would take a sample like a nose swab or get you to spit in something.
And then they would stick it in a tube and try to make a bunch of copies of the target
through a process like PCR, which is used for replicating DNA or RNA molecules.
If that target is present, lots of copies of it will be made. If it’s not, nothing happens.
Then they will also add a CRISPR system with these special Cas proteins
that cut up anything in reach.
And finally, they would add little pieces of DNA called reporter DNA to the sample.
This DNA would have special proteins attached to it
that fluoresce when the DNA is cut.
In theory, if the Cas protein finds its infectious target,
it will start cutting these pieces of nearby reporter DNA as well,
causing the whole test tube to fluoresce!.
And that fluorescence will let the doctor know that the target
was present in the original sample. In other words, that the test was positive.
These tests can also be paired with a dipstick, similar to a pregnancy test,
so that you can test for the collateral cleavage and target detection
even without fluorescence equipment.
Today, a number of companies are trying to do this to test
for various diseases, including COVID-19. .
And that is encouraging. Because fast tests could help us bring more tests
to more people, including in remote locations far from a lab
and in settings where results are needed fast.
Today, there are many more people who need organs
than there are available organs for donation.
That leaves many patients in need waiting on long lists for years.
Which is why some scientists are looking beyond human donors
and working on what’s called xenotransplantation.
That’s the idea of transplanting living tissue, cells, or organs
from one species into another.
And it’s not a new idea. People have been receiving
replacement heart valves from pigs for over 30 years.
In fact, any animal with organs of similar sizes and functions to human organs
could hypothetically make a good donor.
Pigs, cows, and baboons are all in the running!
But xenotransplantation is risky.
For instance, numerous attempts to replace human kidneys with pig kidneys
have ended with the immune system attacking the foreign organ.
In theory, you could get around that by using human tissue
to grow organs inside a pig.
But the pig genome contains the DNA of retroviruses,
which are viruses that insert themselves into their host’s genome.
And these viruses have been shown to spread into human cells in the lab,
where they could cause cancer or issues with the immune system.
The thing is, pigs are an especially attractive option for xenotransplantation
because their organs are fairly similar to ours, and because we really know quite well
how to raise them because we do it all the time,
so scientists have been trying to make this work.
And thanks to CRISPR, it’s looking more and more possible.
Since the CRISPR system can target specific parts of the genome,
scientists have been able to program it to target the 62 retroviruses found in pigs.
CRISPR basically chops up the viral DNA sequences in the pig’s genome
so that the genetic code is broken. That makes it much less likely for those viruses
to spread to human cells during a transplant.
Scientists then created embryos from these modified pig cells
and placed them into surrogates to create pigs with inactive viruses.
Now, it’s still a work in progress. Researchers still need to find better ways to avoid
rejection by the immune system, but it’s a step in the right direction.
Organs from these pigs have the potential to be much safer
for xenotransplantation into humans.
Finally, not only can CRISPR potentially help with illnesses on an individual level,
it’s also considered as a possible solution to larger-scale health problems.
See, many diseases spread through vectors, which are organisms like
mosquitos, fleas, and ticks that carry and transmit diseases to us.
So, one way to tackle these diseases is to control their spread among vectors,
before they even get to us.
For instance, Lyme disease is caused by a bacterium called Borrelia burgdorferi,
which gets transmitted to humans through blacklegged ticks.
But ticks get the bacteria by feeding on infected mice.
So if we could control the spread of the disease among mice,
we could potentially protect a lot of humans.
And that’s where CRISPR comes in.
Now, you could technically use CRISPR to try and attack the bacteria,
or try and eliminate the ticks, but it would be pretty impossible
to find and treat every bacterium or tick in the forest!
Instead, in a project called Mice Against Ticks, scientists are trying to engineer
the genomes of mice using CRISPR to make mice immune to Lyme disease.
Because if mice can’t pick up the disease,
they can’t give it to ticks and the ticks can’t give it to us.
It would still be close to impossible to catch and immunize
every mouse in a given population.
But the researchers’ idea is to start out by focusing on mice
on islands like Nantucket and Martha’s Vineyard,
where mouse populations can be easily controlled and studied.
Some mice already have a genetic resistance to Lyme disease,
so the first step would be to identify those.
Then the scientists plan to use CRISPR to insert
those naturally evolved genes into more mice in the lab.
Because CRISPR systems don’t only make cuts.
They can also be used to make insertions.
See, once a piece of DNA is cut, the cell will try and repair it itself.
But scientists also can give the cell a piece of DNA to repair itself with,
thereby inserting a new section of DNA into the break.
And that’s what they plan to do here.
Then they’d breed those mice until they had around 100,000 that were immune.
Finally, they would release these mice onto the island
at a time when normal mouse populations are low
in order to spread the gene into the population as quickly as possible.
If all goes well, it could drastically reduce the spread of Lyme disease—
all by controlling the vector rather than the disease itself.
All of these applications are just a tiny fraction
of the new ways that CRISPR is being used!
In fact, over 5000 papers on CRISPR were published this year alone.
And as research progresses, CRISPR has enormous potential
to change our future for the better in all sorts of unimaginable ways.
Thanks for watching this episode of SciShow!
And now that you’ve seen some of what CRISPR can do beyond gene editing,
if you want to learn more about its power as a gene editor,
you can check out our video on that next!
[♪ OUTRO]