David R. Liu: Can we cure genetic diseases by rewriting DNA?
David R. Liu leads a research group that combines chemistry and evolutionary techniques to create revolutionary new medicines. Full bio
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your mother and father ever gave you
of three billion letters of DNA
with three billion components,
made by your cells,
or base, such as C,
such as T, G or A.
will collectively accumulate
which are also called "point mutations."
point mutations are harmless.
an important capability in a cell
in harmful ways.
from your parents
in your development,
that many or all of your cells
of hundreds of millions of people
or Tay-Sachs disease.
caused by point mutations
the exact single-letter change
and, in theory, could cure the disease.
a single A to T point mutations
are born with a T
that these wonderful, bright kids
by about age 14.
to efficiently correct point mutations
T back into a C.
in developing such a capability,
as sources of infection,
prone to being infected,
to fight viral infection.
is now better known as CRISPR.
is this purple protein
scissors to cut DNA,
between bacterial and viral DNA,
programmed to search for,
a virus for the first time,
of that virus's DNA
to direct the CRISPR scissors
during a future infection.
the function of the cut viral gene,
the virus's life cycle.
Emmanuelle Charpentier, George Church,
could be programmed
chosen by bacteria.
of the cut gene, typically,
of random mixtures of DNA letters
useful for some applications.
that cause genetic diseases,
won't benefit patients,
needs to be restored,
already-mutated hemoglobin gene
to make healthy red blood cells.
new DNA sequences into cells
surrounding a cut site,
in most types of cells,
I've dreamed of a future
or maybe even cure
to fix point mutations,
working with my students
directly on an individual DNA base,
the mutations that cause genetic diseases.
are molecular machines
searching mechanism of CRISPR scissors,
one base to another base
CRISPR proteins as molecular scissors,
one DNA letter into another
the atoms of one DNA base
the first base editor, shown here,
from the same organism.
and disabling the ability to cut DNA
and bind a target DNA sequence
scissors, shown in blue,
on the DNA base C,
that behaves like T.
to the first two proteins
from being removed by the cell.
allows us to convert Cs into Ts
our work was only half done.
have to form base pairs.
on one DNA strand creates a mismatch,
by deciding which strand to replace.
this three-part protein
as the one to be replaced
of what used to be a C-G base pair
in the lab, Alexis Komor,
this first class of base editor,
disease-associated point mutations,
that this first base editor can reverse
or 5,000 or so pathogenic point mutations.
of disease-causing point mutations
a second class of base editor,
As into Gs or Ts into Cs.
a former post doc in the lab,
this second class of base editor,
almost half of pathogenic point mutations,
the rapid-aging disease progeria.
borrow, once again,
to the right site in a genome.
an incredible problem;
A into G or T into C
look for another project,
of a naturally occurring protein
our own protein in the laboratory
that behaves like G,
that performs related chemistry on RNA.
survival-of-the-fittest selection system
of protein variants
chemistry to survive.
scissors, shown in blue,
the nonedited T with a C
of an A-T base pair to a G-C base pair.
interrupted by applause.
first two classes of base editors
and one and a half years ago.
by the biomedical research community.
more than 6,000 times
1,000 researchers around the globe.
have been published already,
ranging from bacteria
human clinical trials,
a critical milestone towards that goal
that cause human genetic diseases.
led by Luke Koblan and Jon Levy,
that second base editor
T back into a C
at the DNA, RNA and protein levels.
been used in animals
correcting a point mutation
single DNA letter changes
to probe the role of individual letters
with diseases such as cancer.
Beam Therapeutics and Pairwise Plants,
to treat human genetic diseases
than the past three years:
its full potential
with genetic diseases.
are thought to be treatable
of cells in an organ,
like base editors
to deliver base editors
that give you a cold
new molecular machines
to another base pair
at off-target locations in cells
doctors, ethicists and governments
that base editing is applied thoughtfully,
even just five years ago
an individual base pair
in the human genome
of other outcomes,
are you reading?"
group of students
what we could design ourselves
to evolve what we couldn't,
that science-fiction-like aspiration
we give our children
three billion letters of DNA,
and repair them.
ABOUT THE SPEAKERDavid R. Liu - Chemical biologist
David R. Liu leads a research group that combines chemistry and evolutionary techniques to create revolutionary new medicines.
Why you should listen
During his PhD research at Berkeley, David R. Liu initiated the first general effort to expand the genetic code in living cells. As a professor at Harvard and the Broad Institute, Liu integrates chemistry and evolution to illuminate biology and develop next-generation therapeutics. He has published more than 170 papers and is an inventor on more than 65 issued US patents.
Liu's major research interests include development and use of genome editing technologies to study and treat genetic diseases; the evolution of proteins with novel therapeutic potential; and the discovery of bioactive synthetic molecules using DNA-encoded libraries. Base editing, phage-assisted continuous evolution (PACE) and DNA-encoded libraries are three technologies pioneered in his laboratory that are now widely used in the biomedical sciences. Liu has also cofounded six biotechnology and therapeutics companies, including Editas Medicine, Beam Therapeutics, Pairwise Plants and Exo Therapeutics.
Liu grew up in Riverside, California, where playing with insects in his backyard crystallized his interest in science. He also is passionate about photography and has been banned from playing blackjack at virtually every major casino in Las Vegas after developing a creative and highly advantageous card-counting system.
David R. Liu | Speaker | TED.com