- [Roxanne Makasdjian, UCBerkeley] Work to improve
techniques for editing DNA,
the code of life has just seen
an important new
development at UC Berkeley.
Researchers Basem Al-Shayeb
and Patrick Pausch have discovered CasPhi.
It's a protein that may make
the technique, CRISPR, that has
recently accelerated
gene-editing research,
even more effective for
treating genetic diseases
in the future and improving agriculture.
The team's discovery was sort
of hiding in plain sight.
- [Al-Shayeb] We recently discovered
these giant bacterial viruses,
or huge phages as we called them.
These viruses, we found them
in many different environments -
from hot springs in Tibet,
to baboons in Kenya,
to moose in Alaska.
They're found pretty much
everywhere, and they have DNA
that is up to 15 times larger than
the average bacterial virus.
I mean, it was mind blowing to us to
even find these to begin with,
that they have such long strands of DNA,
But also that they're found
pretty much everywhere
and went undetected for so long.
- [Makasdjian] Even more striking is that these
viruses carry with them an unexpected
and powerful ability.
- [Al-Shayeb] We found that they
encode CRISPR cast systems
or an immune system that bacteria
naturally use to fend off viruses.
- [Makasdjian] Bacteria keep a record
of the viruses that infect them.
And then they use a
protein, Cas9, to recognize
and disable those viruses
the next time they show up.
Based on their discovery of this system,
Berkeley scientists developed
the CRISPR-Cas9 tool
to locate and cut DNA at precise points.
Now, finding that a similar system
exists in viruses themselves, was stunning.
- [Al-Shayeb] Why in the world would
a huge bacterial virus carry
a system that kills viruses?
And what we found is that this huge phage
or these giant bacterial
viruses will attach
to the bacterial host
and inject their DNA.
- [Makasdjian] That injected DNA
contains a code prompting
the host bacteria to
make the protein CasPhi.
CasPhi's job is to attack
other competing viruses.
This whole scenario - 
orchestrated by the giant virus.
- [Al-Shayeb] So, in a way,
it's protecting its host.
But only because it wants to keep it
and its resources to itself.
- [Makasdjian] Gene-editing
with the CRISPR system
works this way:
Scientists usually use the protein, Cas9,
pair it with an RNA sequence that matches
the DNA sequence that needs to be changed.
The RNA-Cas9 pair locates the target DNA
and cuts it with a chemical reaction.
The cell then can repair its own DNA
or the correct DNA
sequence can be inserted.
But researchers found that
the new protein they discovered, CasPhi,
is a lot smaller than Cas9,
which might actually be
an advantage for use in gene-editing.
- So what's interesting is that
we found this CRISPR casPhi
system is about half the size of Cas9,
And it can be used with a much smaller
RNA strand to find its target
and cut that target DNA.
- [Makasdjian] This could
help alleviate one of the
difficulties of using Cas9
to correct genetic diseases.
- [Al-Shayeb] Delivery is a key obstacle
in trying to use this as a therapeutic.
Because Cas9 is such a large protein,
It has to be split up
into different packages,
and you hope that they
all reach the same address
in the body to perform the therapy.
Patrick, the co-first author of the paper
found that the protein
is able to multitask,
cut the targeting DNA,
but also develop the guiding
RNA system to locate the DNA
to cut, within one site in the protein.
And that hasn't been seen before.
- [Makasdjian] CasPhi promises another
practical advantage over Cas9.
- [Al-Shayeb] Some people seem to have antibodies
that would reject the treatment.
But with CasPhi, because it
comes from a bacteria or virus,
and bacteria or viruses aren't
shown to cause this kind of
allergic reaction in the body,
we don't expect the CasPhi to be rejected.
- [Makasdjian] The team looks
forward to further testing
of their new CRISPR-CasPhi system.
- [Al-Shayeb] We've shown that it
can perform gene-editing
in human cells, but also in plant cells.
It's very tiny, but it's mighty.
