High-Throughput Screening, CRISPR & Immunotherapy - The Sidi Chen Lab at Yale School of Medicine

Transcript

• 00:05Immunotherapy
• 00:07is, by definition, the therapy
• 00:09to harness the immune system
• 00:11as therapeutics.
• 00:12It utilize
• 00:13your own cells
• 00:15and turn them into
• 00:17disease fighting drugs.
• 00:19Our own cells
• 00:21are also controlled by our
• 00:22own genome. So we have
• 00:25a three billion
• 00:26base pair genome that encodes
• 00:28the secret of life that
• 00:30governs the development, the morphology,
• 00:33your height,
• 00:34your behavior, and diseases when
• 00:36they go wrong.
• 00:37So
• 00:39our own cells
• 00:40that we utilize in neurotherapy
• 00:42to stimulate, to attack cancer
• 00:44cells,
• 00:45they're also governed by those
• 00:46genes.
• 00:47So in order to understand
• 00:49how immunotherapy work, we need
• 00:50to know how the genes
• 00:52work in in order to
• 00:53control the immune cells.
• 00:58We try to understand what
• 00:59genes control what immune cells
• 01:01in what disease settings
• 01:04in a systems manner, which
• 01:06means, broadly speaking, we look
• 01:08at every gene,
• 01:10every molecule,
• 01:11and all the possible cell
• 01:13types,
• 01:14trying to understand what are
• 01:15the key problems of immunotherapy
• 01:18and how we can overcome
• 01:19them.
• 01:23One of the most canonical
• 01:26approach we utilize is unbiased
• 01:28genetic screens.
• 01:29With the technology breakthroughs such
• 01:32as CRISPR gene editing,
• 01:34we can now edit every
• 01:35human genes in our hands
• 01:37in a massive parallel fashion.
• 01:39So we can perturb all
• 01:41the twenty thousand genes in
• 01:42your genome or every possible
• 01:44base you're interested in, and
• 01:46then see which genes, when
• 01:48you perturb, would have an
• 01:49effect
• 01:50influencing the outcome of immunotherapy.
• 01:52And then you can develop
• 01:54new therapy targeting those genes
• 01:55that we identified.
• 01:57So we utilized the shotgun
• 01:59approach, which is
• 02:01in vivo
• 02:03high throughput crystal screen,
• 02:05and we mutate every gene
• 02:06possible,
• 02:07and we eventually came up
• 02:09with a smaller number of
• 02:10genes that we believe truly
• 02:12have a profound effect on
• 02:14the immune cells function.
• 02:15And those, if we hit
• 02:17them,
• 02:18we can potentially develop novel
• 02:20novel therapeutics.
• 02:24The way we develop therapeutics,
• 02:27we call the gene editing
• 02:29for
• 02:30NS immunotherapy.
• 02:31For the first bucket,
• 02:33we utilize gene editing to
• 02:35discover novel targets and then
• 02:37we hit it with a
• 02:38traditional modality such as small
• 02:39molecule or antibodies.
• 02:41And the second approach is
• 02:43that for those quote unquote
• 02:45undruggable or difficult to drug
• 02:47targets, we we don't need
• 02:48to make a molecule. We
• 02:50can directly
• 02:51edit these genes
• 02:53inside the genome of the
• 02:54cell,
• 02:55and we utilize those cells
• 02:57as therapeutics.
• 02:58And finally, what do I
• 03:00mean by gene editing as
• 03:01immunotherapy,
• 03:02right? I mean,
• 03:03forget about the traditional approach,
• 03:05forget about the cells, let's
• 03:07deliver the whole machinery of
• 03:08gene editing
• 03:09into the body as a
• 03:10gene therapy and let that
• 03:13stimulate or
• 03:14manipulate
• 03:15or fine tune the immune
• 03:16system so they can attack
• 03:18cancer or they can treat
• 03:20diseases.
• 03:21So those are the three
• 03:22buckets of how we develop
• 03:23new therapeutics.