 
- [Patrick] One of the
central challenges that we're
trying to solve in molecular biology,
is how can we rapidly
and precisely manipulate
the bio molecules that talk to
each other inside of a cell.
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- Working at the intersection of biology
and technology development,
my lab seeks to invent
new genetic engineering tools,
that we hope will pave
the way for new kinds of
gene and cell therapies.
So over just the last few years,
there's been a real explosion
in the sequencing of genomes of microbes
from all over the planet.
And this vast amount of
data is largely untapped,
so we've looked in these
sequences for new CRISPR systems.
Which are really bacterial immune systems
that are central to how these
bacteria defend themselves
against their forms of viruses.
In this new study, we
discovered new CRISPRS
that naturally target
RNA to develop a tool
for RNA engineering.
This is distinct from our
other work on CRISPR Cas9,
which uses a DNA-targeting
molecular scissors.
The DNA in your cells
are largely the same,
whereas the RNA product
is really what's changing.
And mediates dynamic processes
like inflammation or behavior,
and in fact many genetic
diseases are actually caused
by defects directly at the RNA level.
And so by targeting RNA we can start
to try to manipulate these processes.
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- After we found that the
system that we discovered,
really does in fact target
RNA, we wanted of course
to transfer it to human cells,
to actually modulate the
RNA messages in those cells.
The RNA messages inside
the cell are not always
just translated into a
single protein product.
Sometimes a single RNA
can be used to be turned
into different kinds of proteins,
through a process called splicing.
What splicing does, it basically
modifies the RNA message
to turn into two different
kinds of proteins, for example.
And this balance of these two
different types of proteins
is dysregulated in certain diseases,
like neurodegeneration.
Neurodegeneration is just
another term for dementia.
In one particular type
of neurodegeneration,
called frontal temporal dementia,
the protein called TAU is changed,
the TAU transcript can be translated into
two different types of TAU protein.
And in a healthy cell, there's
a very finely controlled
balance between those two
different types of TAU proteins.
In the diseased cell one type of protein
now is dominating, and
more than it should be,
so by using our RNA targeting CRISPR protein,
to target specific elements
inside the RNA message,
we're able to reset the balance between
these two kinds of TAU proteins.
- I think we're really
only scratching the surface
of what we can do with these
genetic engineering tools.
And by targeting RNA, the
hope is we can develop
new types of intelligent
therapies that can
respond to the state of a cell,
and not just the genome that encodes it.
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