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Good evening.

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(Applause)

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Tonight I want to talk to you
about a new area of nanotechnology;

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that is nanomedicines.

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And this is an area

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where nanotechnology is enabling
new and exciting biotechnology.

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Now, over the past few decades,

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deaths due to heart disease
have plummeted,

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as you can see
from the data on this slide,

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and that's a really good story.

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But unfortunately with cancer, 
we can't say the same.

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And so today,

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cancer is now the number one disease
that kills Americans under the age of 85.

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And as you might expect,
this is not just a US problem;

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it's a worldwide problem.

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And from these data, you can see 
that the death rate due to cancer

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exceeds that from tuberculosis, 
malaria, and HIV all combined.

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And unfortunately, it's predicted
to continue to increase in the future.

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So if you look, cancer has
a massive cost to society right now

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in the loss of productivity that we have
from people expiring at an early age,

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but also in the cost of the therapies,

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as these therapies are increasing in price
at rates that are just not sustainable

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when we have to treat
so many people worldwide.

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And, of course, 
you've probably all witnessed

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that many patients
that are on current therapies

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really suffer through poor quality of life
while they're on treatment

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and even after the treatment's over.

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So there's a real strong reason
to try to develop new cancer therapeutics

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that are efficacious,
that have reasonable costs,

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and, of course, can give patients
high quality of life.

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And these issues motivate us
every day of our life.

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We get up, go to the lab,
go to the hospital

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to try to see if we can make
an impact on these issues.

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Now, if we really want to have
an impact on the death rate,

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we're going to have to treat
what's called metastatic disease.

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That's where you have multiple tumors
throughout the body at the same time,

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and this implies that your therapy has
to treat the whole body at the same time

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or it's called systemic treatments.

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Now, what are nanomedicines?

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Well, these are small particles
that are therapeutics,

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and they have the potential

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to try to change the way
that we treat cancer patients.

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Now, the National Cancer Institute
defines these particles

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as particles between
one and 100 nanometers,

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and they're composites
between therapeutic agents

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and other carrier molecules,
like polymers.

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Now, why is the size important?

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This is real nanotechnology.

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These particles are small.

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So if you take 100-nanometer particle 
and increase it to a soccer ball,

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that's the same increase in size 
from the soccer ball to the planet Earth.

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So these very, very small particles,
we can put into the blood of a patient,

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and they will circulate
throughout your body.

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Now, it's interesting
that it's nanotechnology,

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but it's actually large relative
to these chemotherapeutic drugs

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that are less than a nanometer in size.

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And so the analogy
is that the drug is the soccer ball;

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the nanoparticle is actually
the Goodyear blimp.

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So it's a very large entity,

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and because of that, it's restricted
from certain areas in your body.

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It also can carry a large payload of drug.

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Think about how many soccer balls you
might be able to put in the Goodyear blimp

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and how other multiple functions
can be put onto these larger entities.

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Now, my group and others
throughout the world

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have spent the last decade or so

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trying to figure out how to design
and engineer these multifunctional systems

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to treat patients with solid tumors.

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And the field as a whole is converging
to this area of about 50 nanometers,

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plus or minus 20.

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And think of 50 nanometers
as, like, half the Goodyear blimp,

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rather than the full Goodyear blimp.

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And I've given you two illustrations
on this slide of those types of particles.

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And so we're trying to design the size
and what's on the surface

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and what kind of functions
that we can place into these particles.

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And the reason is as follows -

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now, the one panel's not showing up -

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is that when you
infuse these into a patient

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they can circulate in the blood system,

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but they can't access certain areas
that chemotherapeutic drugs access,

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like healthy tissues.

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For example, those drugs
can go into your bone marrow,

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that makes all of your cells
for your immune system, and kill them

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and the molecules of your hair
that make your hair fall out.

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With a nanoparticle, they can't go there,

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and so they're much safer therapies
than the chemotherapeutic drugs.

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But tumors grow new vessels, and so
those vessels are not completed yet,

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and they'll allow these nanoparticles
to actually access that region.

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And so we decorate
the surface of these particles

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with molecules that allow them
to preferentially act

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and interact with surface molecules
on the cancer cells

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that then take these particles 
inside the cell.

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The ones we make at Caltech,
we try to make somewhat intelligent;

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we put chemical sensors on them that say,

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"Okay. I'm inside the cell now.

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Give off my therapeutic payload."

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And we make, by design, 
the remnants of this particle small enough

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that when it disassembles,
those remnants go out into your urine,

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so there's no trace of it left
after the administration.

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So normal cells grow, they divide,
and they die in an orderly fashion.

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And there are many
regulatory systems that are used

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that are turned on
and turned off to control this.

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In cancer, some of these are altered,

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and so what can happen, for example,

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is the pathways that allow
these cells to grow and divide

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get turned on permanently.

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So if you really want to make an effective
therapy that has minimal side effects,

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you'd like to attack 
just at those altered positions.

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And there's some new biotechnology
that may help us do this job,

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and this is called RNA interference,
and it's a method to silence genes,

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where the drug, now, is a small piece
of what's called a duplex of RNA -

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two strands of RNA together.

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And Craig Mello and Andy Fire

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got the Nobel Prize in Physiology
or Medicine in 2006

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for figuring out how this works in worms.

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But when Andy gave his Nobel address,

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he said, "Well, what could happen
if we have a patient that has a tumor

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and there's a gene 
that's causing that tumor to grow?

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Could we, in fact, 
make one of these small RNAs

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and, in fact, give it to the patient
and stop the growth of the tumor?

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If you could get that RNA to the target,

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you could have some
really cool therapeutics."

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I like that term, "cool therapeutics."

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And delivery is the major issue:

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How do you get these to the right place
and to do the right job?

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So, about a year or so ago,

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my colleagues and I were the first to show

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that you could translate this
from a worm to a human,

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and as you might expect,
that's a big translation.

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But just last year,

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we were able to show that you can, 
in fact, do this in patients,

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and so I'll try to illustrate
a few points for you now.

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So what is so interesting
about this technology

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is, unlike most drugs
that attack at the protein level -

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and proteins do many different functions,

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so you have to have drugs
that do many different things,

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and there are lots of protein functions
that you just can't attack,

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and those are called undruggable targets.

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But RNA interference attacks
at what's called the messenger RNA,

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and all we have to do there
is just change the sequence of the letters

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that we can attack and eliminate
any of those messenger RNAs,

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and so any gene, now, 
is druggable by this technology,

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just by changing
the letters on our duplex RNA.

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So what my colleagues and I did

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is we developed a nanoparticle
that carried these small RNAs,

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and we infused these into cancer patients.

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And these particles would circulate
through the body of the cancer patients.

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And we were able to show

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that they would, in fact, go to tumors 
in metastatic melanoma patients,

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and, in fact, they would do it
in a dose-dependent fashion,

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and what that means

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is the more nanoparticles
that we actually put into the body,

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the more we saw ending up in the tumors.

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And we could do this where patients
would have very high quality of life.

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In the few patients
that we were able to get biopsies,

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we were able to look more closely,

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and I've shown two pictures
here on this slide:

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the first is, the light areas 
that are in the tumor area,

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those are actually the nanoparticles.

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And so we were actually able to show
that these nanoparticles go into the tumor

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and into the tumor cells,

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but they didn't localize at all
into the healthy tissue

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that was around the tumor,
as we're trying to do.

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Now, we were able to eliminate
this individual messenger RNA.

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We were able to show that it was
by this RNA interference mechanism.

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And so, it would stop
the production of a protein,

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which I'm showing on this slide as well -

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that we eliminated this protein,

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and this caused the tumors
not to grow in these patients.

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So, what I've shown you
is at least one example

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where, in fact, the nanoparticle
can enable this new biotechnology

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to try to create new cancer therapeutics
with the right type of properties.

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And so we hope that
the potential for these is high

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and mainly to be able
to give cancer patients

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treatment options
with high quality of life.

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Now, what about the future?

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So what we've been able to do so far

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is to take these nanoparticles,
infuse them in the patient,

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and actually inhibit an individual gene
in the tumor of these patients

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while they're having high quality of life.

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Now, there's no reason

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that we couldn't put multiple types 
of RNAs into these particles

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so we could attack
multiple genes simultaneously.

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So, our vision is that
we start to treat patients

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and that we use, then, 
a fingerprick of blood

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and analyze a variety
of biomolecules in blood

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through a variety of other techniques
that people have talked about -

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various arrays and so forth.

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We take that information -

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probably what will happen in the future
is you'll do this at home;

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you'll plug it into your iPhone,

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and your iPhone
will call up your physician

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and say, "Here are the results"

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so that the next time 
you go to the doctor's office,

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they're going to say,

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"Here's the new therapy
that we're going to give to you."

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So not only in a personalized sense 
can you change for these therapies,

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but we're hoping that you can
actually change in a dynamic sense

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for an individual person to actually
follow the course of the disease

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and eradicate it
in the best manner you can.

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So that's the vision for cancer,
and it probably would happen that way -

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and then hopefully
with other diseases as well.

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Thank you.

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(Applause)