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Hi, I'm David Schaffer.
I'm a professor of chemical
and biomolecular engineering,
bioengineering, and
molecular and cell biology
at the University of
California at Berkeley,
where I also serve as the
director of two institutes,
QB3 as well as Bakar Labs.
Today, it's my pleasure
to be sharing with you
some of our work
and perspectives
in the directed evolution of AAV delivery
systems for clinical gene therapy.
0:24
I'd like to start with
what really motivates us
and gets us out of
bed every morning,
which is that regardless of which
tissue you look at in the human body,
there are very, unfortunately, long-term
chronic degenerative disorders
that kill off particular
populations of cells,
gradually undermine the
function of those tissues,
and rob patients their
quality of life.
Using the central nervous
system as an example,
there are a couple of different
categories of diseases.
There are monogenic disorders,
where you can sequence a
specific gene in the genome
to find the mutation that's
responsible for a given disease,
and that includes lysosomal
storage diseases,
as well as Huntington's.
In addition, there more
complex idiopathic disorders,
such as Alzheimer's
and Parkinson's,
that are due to a
combination of genetics,
as well as experience
and environment.
Regardless, however,
the underlying cause,
we really need to identify
novel therapeutics
to be able to spare the life
as well as quality of life of patients
suffering from these conditions.
1:18
To do so, we feel it's useful
to roll all the way back
to a very basic
tenet of biology,
specifically the central
dogma that holds
that information is stored
at the level of DNA,
transcribed into RNA and
translated into protein.
RNA and protein make up the
functional arms of biology,
and information, of
course, is stored at DNA.
1:40
For us, each one of these
levels of information
represents a potential
drug target.
The majority of pharmaceuticals
used in the clinic these days
target at the level of proteins,
where small molecules
float around to find
a hydrophobic collapse
within an enzyme typically,
and inhibit or modify the
activity of that molecule.
By contrast, monoclonal antibodies
float around on the outside of cells
and again, typically, bind to a
protein and inhibit its function.
It's also possible to
drug at the level of RNA.
There are several FDA-approved
RNA interference drugs,
which degrade specific messages.
Antisense drugs
are also approved.
And finally, of course, we know
very well from Pfizer and Moderna
that messenger RNA itself can
be a therapeutic modality.
My career really revolves at the
level of drugging DNA as a molecule.
If you're adding a new gene to
a genome, that's gene therapy.
If you're changing the sequence of an
existing gene, that's a genome edit.
Finally, if you're adding an
entirely new genome to a tissue,
that's cell therapy.
What's potentially promising and
transformative about drugging
at the level of DNA is that, unlike
small molecules and proteins,
DNA can become a permanent
part of an organ or a tissue,
so you can think
about one and done.
Single administration,
long-term therapeutic benefit.
