0:00:00.997,0:00:03.203
Cancer affects all of us,

0:00:03.203,0:00:06.523
especially the ones that come back[br]over and over again.

0:00:06.523,0:00:09.542
The highly invasive [br]and drug-resistant ones,

0:00:09.542,0:00:11.910
the ones that defy medical treatment,

0:00:11.910,0:00:15.440
even when we throw our best drugs at them.

0:00:15.440,0:00:18.365
Engineering at the molecular level,

0:00:18.365,0:00:21.036
working at the smallest of scales,

0:00:21.036,0:00:23.497
can provide exciting new ways

0:00:23.497,0:00:27.491
to fight the most aggressive[br]forms of cancer.

0:00:27.491,0:00:29.992
Cancer is a very clever disease.

0:00:29.992,0:00:32.042
There are some forms of cancer,

0:00:32.042,0:00:36.941
which, fortunately, we've learned[br]how to address relatively well

0:00:36.941,0:00:40.842
with known and established drugs[br]and surgery.

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But, there's some forms of cancer[br]that don't respond

0:00:43.388,0:00:45.115
to these approaches

0:00:45.115,0:00:47.715
and the tumor survives[br]or comes back,

0:00:47.715,0:00:50.316
even after an onslaught of drugs.

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We can think of these[br]very aggresive forms of cancer

0:00:54.333,0:00:57.677
as kind of super villains in a comic book.

0:00:57.677,0:01:00.475
They're clever, they're adaptable,

0:01:00.475,0:01:04.062
and they're very good at staying alive.

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And, like most super villains[br]these days,

0:01:07.290,0:01:12.979
their super powers come from[br]a genetic mutation.

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The genes that are modified[br]inside these tumor cells

0:01:15.881,0:01:21.222
can enable and encode for new[br]and unimagined modes of survival,

0:01:21.222,0:01:23.637
allowing the cancer cell[br]to live through

0:01:23.637,0:01:27.004
even our best chemotherapy treatments.

0:01:27.004,0:01:31.534
One example is a trick [br]in which a gene allows a cell,

0:01:31.534,0:01:34.597
even as the drug[br]approaches the cell,

0:01:34.597,0:01:40.309
to push the drug out before the drug[br]can have any effect.

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Imagine the cell effectively[br]spits out the drug.

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This is just one example[br]of the many genetic tricks

0:01:47.577,0:01:50.200
in the bag of our super villain, cancer.

0:01:50.200,0:01:53.103
All due to mutant genes.

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So, we have a super villain[br]with incredible super powers

0:01:57.724,0:02:01.903
and we need a new and [br]powerful mode of attack.

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Actually, we can turn off a gene,

0:02:05.526,0:02:09.380
the key is a set of molecules[br]known as siRNA.

0:02:09.380,0:02:13.420
siRNA are short sequences[br]of genetic code

0:02:13.420,0:02:17.205
that guide a cell to block[br]a certain gene.

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Each siRNA molecule[br]can turn off a specific gene

0:02:20.582,0:02:23.451
inside the cell.

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For many years since its discovery,

0:02:25.495,0:02:27.468
scientists have been very excited

0:02:27.468,0:02:31.439
about how we can apply[br]these gene blockers in medicine.

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But, there is a problem.

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siRNA works well inside the cell.

0:02:36.037,0:02:39.496
But if it gets exposed to the enzymes[br]that reside

0:02:39.496,0:02:41.540
in our bloodstream or our tissues,

0:02:41.540,0:02:43.769
it degrades within seconds.

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It has to be packaged, protected[br]through its journey through the body

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on its way to the final target[br]inside the cancer cell.

0:02:52.082,0:02:54.659
So, here's our strategy:

0:02:54.659,0:02:58.123
first, we'll dose the cancer cell[br]with siRNA, the gene blocker,

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and silence those survival genes,

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and they'll we'll whap it[br]with a chemo drug.

0:03:02.716,0:03:04.876
But how do we carry that out?

0:03:04.876,0:03:07.825
Using molecular engineering,

0:03:07.825,0:03:11.911
we can actually design [br]a super weapon

0:03:11.911,0:03:13.924
that can travel through the blood stream.

0:03:13.924,0:03:17.066
It has to be tiny enough[br]that it can get through the blood stream,

0:03:17.066,0:03:20.805
it's got to be small enough[br]to penetrate the tumor tissue,

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and it's got to be tiny enough[br]to be taken up

0:03:23.080,0:03:25.240
inside the cancer cell.

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To do this job well, it has to be[br]about one 100th the size

0:03:30.464,0:03:32.438
of a human hair.

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Let's take a closer look[br]at how we can build this nanoparticle.

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First, let's start with [br]the nanoparticle core.

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It's a tiny capsule that contains[br]the chemotherapy drug.

0:03:44.326,0:03:48.390
This is the poison that will[br]actually end the tumor cell's life.

0:03:48.390,0:03:52.198
Around this core, we'll wrap[br]a very thin,

0:03:52.198,0:03:55.054
nanometers-thin blanket[br]of siRNA.

0:03:55.054,0:03:57.093
This is our gene blocker.

0:03:57.093,0:04:00.446
Because siRNA is strongly[br]negatively charged,

0:04:00.446,0:04:04.966
we can protect it with a nice[br]protect layer

0:04:04.966,0:04:07.662
of postively charged polymer.

0:04:07.662,0:04:09.736
The two oppositely charged molecules[br]

0:04:09.736,0:04:12.446
stick together through charge attraction

0:04:12.446,0:04:14.986
and that provides us with [br]a protective layer

0:04:14.986,0:04:18.297
that prevents the siRNA from[br]degrading in the blood stream.

0:04:18.297,0:04:19.946
We're almost done.

0:04:19.946,0:04:21.269
(Laughter)

0:04:21.269,0:04:25.240
But there is one more big obstacle[br]we have to think about.

0:04:25.240,0:04:27.655
In fact, it may be the biggest[br]obstacle of all.

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How do we deploy this super weapon?

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I mean, every good weapon[br]needs to be targeted,

0:04:32.229,0:04:36.293
we have to target this super weapon[br]to the super villain cells

0:04:36.293,0:04:38.266
that reside in the tumor.

0:04:38.266,0:04:42.028
But, our bodies have a natural[br]immune defense system.

0:04:42.028,0:04:44.002
Cells that reside in the blood stream

0:04:44.002,0:04:46.579
and pick out things that don't belong

0:04:46.579,0:04:48.901
so that it can destroy or elinate them.

0:04:48.901,0:04:53.893
And guess that, our nanoparticle[br]is considered a foreign object.

0:04:53.893,0:04:55.797
We have to sneak our nanoparticle

0:04:55.797,0:04:57.841
past the tumor defense system,

0:04:57.841,0:05:04.389
we have to get it past this mechanism[br]of getting rid of the foreign object

0:05:04.389,0:05:06.037
by disguising it.

0:05:06.037,0:05:10.194
So we add one more [br]negatively charged layer

0:05:10.194,0:05:11.541
around this nanoparticle,

0:05:11.541,0:05:13.003
which serves two purposes.

0:05:13.003,0:05:17.253
First, this outer layer is one of[br]the naturally charged,

0:05:17.253,0:05:21.456
highly hydrated polysaccarides[br]that resides in our bodies.

0:05:21.456,0:05:26.448
It creates a cloud of water molecules[br]around the nanoparticle

0:05:26.448,0:05:30.511
that gives us [br]an invisibility cloaking affect.

0:05:30.511,0:05:33.251
This invisibility cloak allows[br]the nanoparticle

0:05:33.251,0:05:36.084
to travel through the bloodstream[br]long and far enough

0:05:36.084,0:05:39.730
to reach the tumor without getting[br]eliminated by the body.

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Second, this layer contains molecules[br]which bind specifically

0:05:46.115,0:05:48.437
to our tumor's cell.

0:05:48.437,0:05:51.830
Once bound, the cancer cell takes up[br]the nanoparticle

0:05:51.830,0:05:57.354
and now we have our nanoparticle[br]inside the cancer cell

0:05:57.354,0:05:59.559
and ready to deploy.

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Alright, I feel the same way,[br]let's go.

0:06:02.186,0:06:04.754
(Applause)

0:06:07.824,0:06:12.493
The siRNA is deployed first.

0:06:12.493,0:06:14.142
It acts for hours,

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giving enough time to silence[br]and block those survival genes.

0:06:19.668,0:06:23.964
We have now disabled those[br]genetic superpowers.

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What remains is a cancer cell[br]with no special defenses.

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Then, the chemotherapy drug[br]comes out of the core

0:06:30.070,0:06:34.482
and destroys the tumor cell[br]cleanly and efficiently.

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With sufficient gene blockers,

0:06:36.804,0:06:39.823
we can address many different kinds [br]of mutations.

0:06:39.823,0:06:45.024
Allowing the chance to sweep out tumors,[br]without leaving behind any bad guys.

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So, how does our strategy work?

0:06:48.511,0:06:53.755
We've tested these[br]nanostructure particles in animals

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using a highly aggresive form[br]of triple negative breast cancer.

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This triple negative breast cancer[br]exhibits the gene

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that spits out cancer drugs[br]as soon as its delivered.

0:07:03.925,0:07:08.012
Usually, doxorubicin, [br]let's call it dox,

0:07:08.012,0:07:10.798
is the cancer drug that is [br]the first line of treatment

0:07:10.798,0:07:12.540
for breast cancer.

0:07:12.540,0:07:18.972
So, we first treated our animals[br]with a dox core, dox only.

0:07:18.972,0:07:21.131
The tumor slowed their rate of growth,

0:07:21.131,0:07:22.594
but they still grew rapidly,

0:07:22.594,0:07:24.946
doubling in size [br]over a period of two weeks.

0:07:24.946,0:07:29.653
Then, we tried our [br]combination super weapon.

0:07:29.653,0:07:34.088
And now layer a particle[br]with siRNA against the chemo pump,

0:07:34.088,0:07:37.106
plus, we have the dox in the core.

0:07:37.106,0:07:41.565
And look, we found that not only[br]did the tumors stop growing,

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they actually decerased in size

0:07:43.956,0:07:46.394
and were elimintaed [br]in some cases.

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The tumors were actually[br]regressing.

0:07:49.970,0:07:52.804
(Applause)

0:07:58.074,0:08:01.905
What's great about this approach[br]is that it can be personalized,

0:08:01.905,0:08:04.576
we can add many different layers[br]of siRNA

0:08:04.576,0:08:08.198
to address different mutations[br]and tumor defense mechanisms

0:08:08.198,0:08:12.169
and we can put different drugs[br]into the nanoparticle core.

0:08:12.169,0:08:15.504
As doctors learn how to test patients[br]

0:08:15.504,0:08:19.158
and understand [br]certain tumor genetic types,

0:08:19.158,0:08:21.294
they can help us determine[br]which patients

0:08:21.294,0:08:22.873
can benefit from this strategy

0:08:22.873,0:08:26.704
and which gene blockers we can use.

0:08:26.704,0:08:29.584
Ovarian cancer strikes [br]a special chord with me.

0:08:29.584,0:08:31.580
It is a very aggresive cancer,

0:08:31.580,0:08:34.320
in part because it's discovered[br]at very late stages

0:08:34.320,0:08:35.853
when its highly advanced

0:08:35.853,0:08:38.709
and there are a number [br]of genetic mutations.

0:08:38.709,0:08:41.797
After the first round of chemotherapy,

0:08:41.797,0:08:46.604
this cancer comes back[br]for 75 percent of patients.

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And it usually comes back[br]in a drug resistant form.

0:08:49.918,0:08:52.149
High-grade ovarian cancer[br]

0:08:52.149,0:08:54.416
is one of the biggest [br]super villains out there.

0:08:54.416,0:08:56.424
And we're now directlng[br]our super weapon

0:08:56.424,0:08:59.653
towards its defeat.

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As a researcher,

0:09:00.907,0:09:04.205
I usually don't get to work with patients.

0:09:04.205,0:09:06.782
But I recently met a mother

0:09:06.782,0:09:12.401
who is an ovarian cancer survivor,[br]Mimi, and her daughter Paige.

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I was deeply inspired

0:09:14.375,0:09:16.488
by the optimism and strength

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that both mother and daughter displayed

0:09:19.646,0:09:23.175
and by their story of courage and support.

0:09:23.175,0:09:26.658
At this event, we spoke about[br]the different technologies

0:09:26.658,0:09:28.609
directed at cancer.

0:09:28.609,0:09:30.861
And Mimi was in tears[br]as she explained how

0:09:30.861,0:09:32.719
learning about these efforts

0:09:32.719,0:09:34.901
gives her hope for future generations,

0:09:34.901,0:09:37.711
including her own daughter.

0:09:37.711,0:09:39.731
This really touched me.

0:09:39.731,0:09:43.307
It's not just about building[br]really elegant science,

0:09:43.307,0:09:46.558
it's about changing people's lives.

0:09:46.558,0:09:49.716
It's about understanding the power[br]of engineering

0:09:49.716,0:09:51.620
on the scale of molecules.

0:09:51.620,0:09:53.709
I know that as students like Paige

0:09:53.709,0:09:55.776
move forward in their careers,

0:09:55.776,0:09:57.239
they'll open new possibilites

0:09:57.239,0:10:00.652
in addressing some of the big [br]health problems in the world,

0:10:00.652,0:10:04.042
including, ovarian cancer,[br]neurological disorders,

0:10:04.042,0:10:06.248
infectious disease.

0:10:06.248,0:10:08.733
Just as chemical engineering[br]has found a way

0:10:08.733,0:10:10.660
to open doors for me.

0:10:10.660,0:10:15.258
Has provided a way of engineering[br]on the tiniest scale,

0:10:15.258,0:10:16.860
that of molecules

0:10:16.860,0:10:19.971
to heal on the human scale.

0:10:19.971,0:10:21.063
Thank you

0:10:21.063,0:10:24.085
(Applause)