[♪ 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]
