A new superweapon in the fight against cancer

Cancer affects all of us,

especially the ones that come back
over and over again.

The highly invasive
and drug-resistant ones,

the ones that defy medical treatment,

even when we throw our best drugs at them.

Engineering at the molecular level,

working at the smallest of scales,

can provide exciting new ways

to find the most aggressive
forms of cancer.

Cancer is a very clever disease.

There are some forms of cancer,

which, fortunately, we've learned
how to address relatively well

with known and established drugs
and surgery.

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

to these approaches

and the tumor survives
or comes back,

even after an onslaught of drugs.

We can think of these
very aggresive forms of cancer

as kind of super villains in a comic book.

They're clever, they're adaptable,

and they're very good at staying alive.

And, like most super villains
these days,

their super powers come from
a genetic mutation.

The genes that are modified
inside these tumor cells

can enable and encode for new
and unimagined modes of survival,

allowing the cancer cell
to live through

even our best chemotherapy treatments.

One example is a trick
in which a gene allows

a cell, even as the drug
approaches the cell,

to push the drug out before the drug
can have any effect.

Imagine the cell effectively
spits out the drug.

This is just one example
of the many genetic tricks

in the bad of our super villain, cancer.

All due to mutant genes.

So, we have a super villain
with incredible super powers

and we need a new and
powerful mode of attack.

Actually, we can turn off a gene,

the key is a set of molecules
called siRNA.

siRNA are short sequences
of genetic code

that guide a cell to block
a certain gene.

Each siRNA molecule
can turn off a specific gene

inside the cell.

For many years since its discovery,

scientists have been very excited

about how we can apply
these gene blockers in medicine.

But, there is a problem.

siRNA works well inside the cell.

But if it gets exposed to the enzymes
that reside

in our bloodstream and our tissues,

it degrades within seconds.

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

on its way to its final target
inside the cancer cell.

So, here's our strategy:

first, we'll dose the cancer cell
with siRNA, the gene blocker,

and silence those viral genes,

and they'll we'll whap (?) it
with a chemo drug.

But how do we carry that out?

Using molecular engineering,

we can actually design
a super weapon

that can travel through the blood stream.

It has to be tiny enough
that it can get through the blood stream,

it's got to be small enough
to penetrate the tumor tissue,

and it's got to be tiny enough
to be taken up

inside the cancer cell.

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

of a human hair.

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

First, let's start with
the nanoparticle core.

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

This is the poison that will
actually end the tumor cell's life.

Around this core, we'll wrap
a very thin,

nanometer-think blanket
of siRNA.

This is our gene blocker.

Because siRNA is strongly negatively charged,

we can protect it with a nice
protect layer

of postively charged polymer.

The two oppositely charged molecules
stick together throough charge attracttion,

and that provides us with a protective
layer

that prevents the sIRNA from
degrading the blood stream.

We're almost done.

(Laughter)

But there is one more big obstacle
we have to think about.

In fact, i tmay be the biggest
obstacle of all.

How do we deploy this super weapon?

I mean, every good weapon
needs to be targeted,

we need to target this super weapon
to the super villain cells

that we find in the tumor.

But, our bodies have a natural
immune defense system.

Cells that reside in teh blood stream

and pick out things that don't belong

so that it can destroy or elinate them.

And guess that, our nanoparticle
is considered a foreign object.

We have to sneak our nanoparticle

past the tumor dfense system,

we have to get it past this mechanism
of getting rid of the foreign object

bu disguising it.

So we add one more negatively charged layer

around this nanoparticle,

which serves two purposes.

First, this outer layer is one of
the naturally charged,

highly hydrated polysaccarides
that resides in our bodies.

It creates a cloud of water molecules
around the nanoparticle

that gives us an invisibility cloaking affect.

This invisibility cloak allows
the nanoparticle

to travel through the bloodstream
long and far enough

to reach the tumor without getting
eliminated by the body.

Second, this layer contains molecules
which bind specifically

to our tumor's cell.

Once bound, the cancer cell takes up
the nanoparticle

and now we have our nanoparticle
inside the cancer cell

and ready to deploy.

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

(Applause)

The siRNA IS DEPLOYED FIRST.

It acts for hours,

giving enough time to silence
and block those survival genes.

We have now disabled those
genetic superpowers.

What remains is a cancer cell
with no special defenses.

Then, the chemotherapy drug
comes out of the core

and destroys the tumor cell
cleanly and efficiently.

With sufficient gene blockers,

we can address many different kinds
of mutations.

Allowing the chance to sweep out tumors,
without leaving behind any bad guys.

So, how does our strategy work?

We've tested these nano-strucutre particles
in animals

using a highly aggresive form
of triple negative breast cancer.

This triple negative breast cancer
exhibits the gene

that spits out cancer drugs
as soon as its delivered.

Usually, ?, let's call it ?

is the cancer drug that is
the first line of treatment

for breast cancer.

So, we first treated our animals
with dox core, dox only.

The tumor slowed their rate of growth,

but they still grew rapidly,

doubling in size over a period of two weeks.

Then, we tried our combination super weapon.

And now layer a particle
with siRNA against the chemo pump,

plus, we have the doxs in the core.

And look, we found that not only
did the tumors stop growing,

they actually decerased in size

and were elimintaed
in some cases.

The tumors were actually
regressin.

(Applause)

What's great about this approach
is that it can be personalized,

we can add many different layers
of siRNA

to address different mutations
and tumor defense mechanisms

and we can put different drugs
into the nanoparticle core.

As doctors learn how to test patients
and understand

certain tumor genetic types,

they can help us determine
which patients

can benefit from this strategy

and which gene blockers we can use.

Ovarian cancer strikes
a special chord with me.

It is a very aggresive cancer,

in part because it's discovred
at very late stages

when its highly advanced

and there are a number
of genetic mutations.

After the first round of chemotherapy,

this cancer comes back
for 75 percent of patients.

And it usually comes back
in a drug resistant form.

High-grade ovarian cancer
is one of

the biggest super villains out there.

And we're now directlng
this super weapon

towards its defeat.

As a researcher,

I usually don't get to work with patients,

but I recently met a mother

who is an ovarian cancer survivor,
Mimi and her daughter pAIGE.

I was deeply inspired

by the optimism and strength

that both mother and daughter displayed.

And by their story of courage and support.

At this event, we spoke about
the different technologies

directed at cancer.

And Mimi was in tears
as she explained how

learning about these efforts

gives her hope for future generations,

including her own daughter.

This really touched me.

It's not just about building
really elegant science,

it's about changing people's lives.

It's about understanding the power
of engineering

on the scale of molecules.

I know that as students like Paige

move forward in their careers,

they'll open new possibilites

in addressing some of the big
health problems in the world.

Including, ovarian cancer,
neurological disorders,

and infectious disease.

Just as chemical engineering
has found a way

to open doors for me.

Has provided a way of engineering
on the tiniest scale

that of molecules

to heal on the human scale.

Thank you

(Applause)