How mRNA Medicine Will Change the World | Melissa J. Moore | TED

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Now, many of the people watching this talk

Mnogi ljudi koji gledaju ovaj govor

by now will have had one, two, three or even four doses

do sada su verovatno dobili jednu, dve, tri ili čak četiri doze

of a messenger RNA vaccine.

mRNA vakcine.

With billions of these shots now in arms.

A sada kada su milijarde ljudi već primili vakcinu,

it’s clear that this new way of making vaccines

jasno je da ovaj novi način pravljenja vakcina

is both remarkably safe and incredibly effective.

veoma bezbedan i efikasan.

But did you know it's not the vaccine itself that's keeping you safe?

Ali da li ste znali da nije vakcina ono što vas štiti?

It's actually you.

To ste u stvari vi.

Because the human body has amazing powers

Zato što ljudsko telo ima sposobnost

to both prevent and cure disease by making its own medicines.

da spreči i izleči bolesti tako što pravi sopstvene lekove.

You just need to know what medicine to make.

Samo treba da znate koji lek želite da napravite.

And that's what your vaccine gave you.

I to je ono što vam je vakcina dala.

Simply a set of instructions

Samo je potreban komplet instrukcija

for how to protect yourself against SARS-CoV-2.

koji govori kako da se odbranite od SARS-CoV-2.

Now vaccines are only the beginning.

Vakcine su tek početak.

As I said before, the advent of mRNA vaccines

Kao što sam i rekla, napredak mRNA vakcina

is heralding in an entirely new era of medicines.

dovodi do potpuno nove ere u lečenju bolesti.

mRNAs give us the ability to not only prevent disease

mRNA vakcine daju nam sposobnost ne samo da sprečimo bolesti

but also treat previously intractable disorders.

već i da lečimo prethodno teške bolesti.

But before I get to that,

Ali pre toga,

let's talk about what is this new way of medicines really about?

porazgovarajmo o čemu se uopšte radi u ovom novom tipu lekova.

Well, it all comes down to proteins.

Sve se svodi na proteine.

Now, you may think of protein

Verovatno mislite da su proteini

as simply something that you need to eat,

samo nešto što morate da jedete

an important part of your diet,

kao bitan deo vaše dijete,

something that's important for you to build muscle.

nešto što je bitno za vas da povećate mišiće.

But it's not just muscle that contains protein.

Ali nisu mišići jedini koji sadrže proteine.

Protein makes up a huge fraction of the incredibly complicated ecosystem

Proteini čine ogroman deo neverovatno kompleksnog ekosistema

that's your entire body.

koji je čitavo vaše telo.

In many ways, your body functions like a large city,

Na razne načine vaše telo funkcioniše kao jedan veliki grad,

full of myriad buildings, interconnected buildings,

sa bezbrojnim zgradama međusobno povezanim,

with lots of different structures.

sa mnogobrojnim različitim strukturama.

Now, just as the word "building"

Kao što reč zgrada ne može da obuhvati raznolikost

fails to capture the incredible variety of structures that make up any large city,

struktura koje čine jedan veći grad, tako i termin protein

the generic term "protein" gives no clue

ne može da dočara raznolikost molekularnih struktura

as to the incredible variety of molecular architectures

at the molecular level.

na molekulskom nivou.

Like buildings, proteins are not monolithic.

Kao i zgrade, telo se ne sastoji od samo jednog dela.

Our body makes many proteins.

Naše telo pravi mnogo proteina.

Some, like the collagen in our skin

Poput kolagena u našoj koži,

that makes our skin tough but pliable.

koji čini našu kožu čvrstom i gipkom.

Like the actin and myosin in our muscles that enable us to move.

Kao aktin i miozin u mišićima koji nam omogućavaju da se krećemo.

Or our blood is full of hemoglobin, ferrying oxygen around.

Ili hemoglobin u krvi koji transportuje kiseonik.

Antibodies protecting us from disease,

Antitela koja nas štite od oboljenja

and clotting factors that close up our wounds.

i mehanizmi zgrušavanja koji zatvaraju rane.

And for any of you that have ever cracked a biochemistry textbook,

I za sve vas koji su nekad otvorili udžbenik iz biohemije,

this should look familiar.

verovatno vam je ovo poznato.

This is the metabolic chart of the human body.

Ovo je metabolička mreža ljudskog tela.

These are all of the reactions in your body that are keeping you

Ovo su sve reakcije u vašem telu koje vas održavaju

alive and well right now.

živim i zdravim u svakom trenutku.

And each one of those reactions is catalyzed by a different protein

I svaka od ovih reakcija je katalizovana od strane nekog proteina,

whose names are shown here in blue.

čiji su nazivi prikazani plavom bojom.

So proteins are not only what makes up the bulk of your body,

Dakle, proteini nisu samo ono što čini većinu vašeg tela,

they’re also what make your body tick and keep you well.

oni su takođe odgovorni za mehanizme u vašem telu i da vas čine zdravim.

Now, if we think again about buildings,

Ako ponovo razmislimo o zgradama,

the structures of buildings may look quite different in the end,

strukture zgrada možda izgledaju različito,

but they're all made of a limited set of building materials

ali su sve one napravljene od svega nekoliko materijala,

and which of those building materials are used

a koji su materijali korišćeni,

and how they're arranged, and how they're attached to one another

kako su raspoređeni i kako su međusobno pričvršćeni,

gives the buildings their final form.

daju zgradama njihov konačni oblik.

The same is true of proteins.

Isto važi i za proteine.

If we zoom down to the molecular level,

Ako zumiramo do molekulskog nivoa,

we can see that proteins,

možemo da vidimo da ako proteine

if we unravel their three-dimensional architecture,

prikažemo kao trodimenzionlne strukture,

are actually just long strings of building blocks.

oni su ustvari samo dugačke linije gradivnih blokova.

And these building blocks have different shapes

A ti gradivni blokovi imaju različite oblike

and different propensities to interact with one another.

i različite sklonosti za međusobnu interakciju.

So it's which building blocks are used

To znači da gradivni blokovi koji se koriste

and the order in which they are in the chain

i njihov redosled u lancu

that gives a protein is three-dimensional shape.

je on što daje proteinu njegov trodimenzionalni oblik.

Now here I'm only showing three proteins,

Ovde prikazujem samo tri proteina,

but creating and maintaining a healthy human

ali da se napravi i održi jedan zdrav čovek

requires the combined action

potrebno je učestvovanje

of over 100,000 different types of protein.

preko sto hiljada različitih tipova proteina.

And our bodies make them all.

I naše telo ih proizvodi sve.

Thus our bodies are remarkable protein factories.

Stoga su naša tela izuzetne fabrike proteina.

At the molecular level, the numbers are truly mind-blowing.

Na molekulskom nivou, brojke su stvarno zapanjujuće.

Each of the 30 trillion cells in your body --

Svaka od 30 triliona ćelija u vašem telu,

that's three with 13 zeros --

što je broj tri sa 13 nula,

contains between one and 10 billion protein molecules.

sadrži između jedan i deset milijardi proteinskih molekula.

That means that you have as many protein molecules in your body

To znači da vi imate isti broj proteinskih molekula u vašem telu

as there are stars in the known universe.

koliko ima zvezda u poznatom univerzumu.

Now each different cell type in your body makes a different kind of protein,

Svaka različita vrsta ćelije u vašem telu pravi različitu vrstu proteina,

a different set of proteins,

različitu garnituru proteina,

like the rods and cones in my eye that are detecting light right now

kao fotoreceptori u mom oku koji detektuju svetlo u ovom trenutku

and the neurons in my brain that are interpreting that light

i neuroni u mom mozgu koji tumače to svetlo

and enabling me to see you right now.

i omogućavaju mi da vas vidim u ovom trenutku.

So they make a particular set of proteins unique to it.

Dakle, oni prave posebnu garnituru proteina.

And like any complex building project,

I kao bilo koji složen građevinski projekat,

you can imagine that the process of protein synthesis

možete zamisliti da proces sinteze proteina

needs to be tightly regulated

mora da bude precizno regulisan

so that the right protein is made at the right time and in the right place.

tako da se odgovarajući protein napravi u pravom trenutku na pravom mestu.

But of course, with anything so complicated,

Naravno, kao i kod bilo čega toliko komplikovanog,

it's perhaps not surprising that there's an occasional mistake,

verovatno nije iznenađujuće da se desi povremena greška,

a fault in the algorithm.

neka greška u algoritmu.

Let's go back to that metabolic chart.

Hajde da se vratimo na metaboličku mrežu.

It’s estimated that one in 1,000 newborns

Procenjuje se da jedno u hiljadu novorođančadi

are born without the ability to make one of the proteins on this chart.

se rodi bez sposobnosti da napravi neki od proteina prikazanih u ovoj mreži.

Therefore, they have lifelong complications

Stoga, oni će imati doživotne komplikacije

due to inborn metabolic errors.

zbog urođenih metaboličkih grešaka.

Let's take just one of those.

Uzmimo samo jedan od ovih.

Let's talk about von Gierke's disease or glycogen storage disease I.

Na primer, von Girkerova bolest ili bolest skladištenja glikogena I.

This is due to the lack of a protein circled here in red,

Nastaje zbog manjka proteina koji je zaokružen crvenom bojom,

whose job it is to release stored sugars

čiji je posao da izbacuje skladišten šećer

so that you can maintain a healthy blood sugar level

da biste mogli da održavate zdravu količinu šećera u krvi

while you're fasting.

dok postite.

So von Gierke's disease patients can't fast.

A to znači da pacijenti sa von Girkerovom bolešću ne mogu da poste.

They must constantly eat small amounts of carbohydrates,

Oni sve vreme moraju da jedu malu količinu ugljenih hidrata,

including getting up every one or two hours during the night

kao i da ustaju svakih sat-dva tokom noći

to eat raw cornstarch.

da jedu sirovi kukuruzni skrob.

Now, imagine the toll that this takes on parents.

Sada zamislite ovo kao obavezu koja je pala na roditelje.

If they are ever to miss a feeding of their child,

Ako ikada propuste da nahrane svoje dete,

their child could slip into severe hypoglycemia,

njihovo dete može dobiti tešku hipoglikemiju,

seizures and possibly death.

iznenadni napad ili može čak umreti.

But even if these patients can keep up this endless feeding cycle,

Ali čak i da ovi pacijenti mogu da održe ovu rutinu,

they are plagued by lifelong complications,

oni će trpeti razne komplikacije,

including delayed puberty,

uključujući odloženi pubertet,

frequent infections, kidney disease and liver cancer.

česte infekcije, bolesti bubrega i rak jetre.

So von Gierke's disease is just one example of a disorder

Von Girkeova bolest je samo jedan od primera bolesti

where we know what protein is missing.

kod kojih znamo koji protein nedostaje.

What if we could give those patients back the ability to make that missing protein?

Šta ako bi tim pacijentima dali mogućnost da sami naprave protein koji nedostaje?

Then we could actually treat their disease instead of just managing their symptoms.

Tako bismo bolest zapravo lečili umesto ublažavali.

And that's where mRNA comes in.

I tu dolazi mRNA.

That's also where I come in.

Tu i ja dolazim.

You see, I spent the better part of my career as an academic

Većinu svoje akademske karijere sam provodila

doing curiosity-based research

radeći istraživanja iz znatiželje

into the fundamental principles of how proteins are made.

o fundamentalnim principima pravljenja proteina.

And my specialty was messenger RNA.

Specijlizovala sam se za informacionu RNK.

Like proteins, messenger RNAs are long chainlike molecules

Kao i proteini, informacioni RNK molekuli su dugački lanci molekula

composed of building blocks.

koji čine gradivne blokove.

The four building blocks that make up messenger RNAs

Četiri gradivna bloka koja čine informacionu RNK

form what is known as the genetic code.

formiraju nešto što se zove genetski kod.

As their name implies,

Kao što ime nagoveštava,

messenger RNAs carry messages:

informaciona RNK prenosi informacije:

messages that are translated by your body in order to create proteins.

informacije koje vaše telo prevede da bi napravilo proteine.

Thus messenger RNAs are the language of life.

Informaciona RNK je jezik života.

And the human body has a lot to say.

I naše telo ima mnogo toga da kaže.

So, like proteins,

Kao i proteini,

your cells are chock-full of messenger RNA.

vaše ćelije su krcate informacionom RNK.

Every one of your 30 trillion cells

Svaka od vaših 30 triliona ćelija

has hundreds of thousands of messenger RNA molecules.

ima stotine hiljada informacionih RNK molekula.

Messenger RNAs are an essential component of all living organisms.

Informacione RNK su neophodne komponente svih živih organizama.

So when you are eating protein-rich foods,

Kada jedete hranu bogatu proteinima,

you're not only eating protein,

ne unosite samo proteine,

you're also eating lots of messenger RNA.

već i mnogo informacione RNK.

Your body takes the messenger RNA in the food that you consumed,

Vaše telo uzima informacionu RNK iz hrane koju ste uneli,

breaks it down into those component parts

razlaže je na komponente

and then builds new messenger RNAs specific to your needs.

i onda gradi nove informacione RNK specifične za vaše potrebe.

Now this continual destruction and rebuilding

Ovaj trajni proces destrukcije i obnavljanja

is a feature true of almost all proteins and messenger RNAs in your body.

je odlika svih proteina i informacione RNK u vašem telu.

Let's take, for example, the circadian clock.

Recimo, na primer, cirkadijalni ritam.

This is the timer in your body

To je sat u vašem telu

that tells you when to be active and when to sleep.

koji vam kaže kada treba da ste budni, a kada treba da spavate.

The proteins that make up this clock

Proteini koji grade ovaj sat

appear and disappear with remarkable regularity every day.

pojavljuju se i nestaju redovno svaki dan.

The way that this is accomplished is that your body makes the messenger RNAs

Način kojim se ovo postiže je da vaše telo napravi informacionu RNK

that encode those proteins

koja kodira te proteine

appear and disappear every day.

tako da se pojavljuju i nestaju svaki dan.

Every day for your entire life,

Svakog dana u vašem životu,

you get your daily dose of clock messenger RNAs

dobijate dnevnu dozu informacione RNK

producing clock proteins.

koja proizvodi te proteine.

Now three properties of proper medicines

Tri svojstva pogodnih lekova

are that their effects are of limited duration,

je da je njihovo dejstvo kratkotrajno,

that their effects are dose-dependent

da njihovo dejstvo zavisi od količine doze

and that they can be given over and over again

i da se mogu davati iznova i iznova

to produce the same effect.

da bi se dobilo isto dejstvo.

mRNA's are transient.

mRNA molekuli su prolazni.

The amount of protein produced

Količina napravljenih proteina

is dependent on how much of that mRNA is present.

zavisi od prisutnog broja mRNA.

And they can be induced over and over again

I oni se mogu izazvati iznova i iznova

to produce the same effect.

da bi se dobio isti efekat.

So wow, it seems so simple.

Ala zvuči jednostavno.

If we could treat a disease,

Ako bismo mogli lečiti jednu bolest,

if there's a protein that's missing to treat a disease,

i ako fali protein koji može da izleči tu bolest,

then we could simply give a few copies of an mRNA to the body

onda bismo mogli samo da damo par kopija mRNA telu

for it to produce that protein.

da bi moglo da proizvede protein koji nedostaje.

If that protein's only needed once,

Ako je taj protein potreban samo jednom,

then maybe a single dose would suffice.

onda možda i samo jedna doza bi bila dovoljna.

If a protein is needed multiple times,

Ako je protein potreban više puta,

then we can dose mRNA over and over again.

onda možemo dati više mRNA doza iznova i iznova.

And that's exactly what's happening.

I to je upravo ono što trenutno radimo.

So when I went on clinicaltrials.gov this morning,

Kada sam jutros otišla na clinicaltrials.gov,

it turns out that there are over 175 clinical trials now open

izgleda da ima preko 175 otvorenih kliničkih ispitivanja

using mRNA-based medicines

koja koriste mRNA lekove

that are recruiting patients.

i koja regrutuju pacijente.

Another 54 clinical trials are waiting in the [wings],

I još 54 klinička ispitivanja čekaju da budu odobrena.

ready to be opened.

So there is a coming tsunami of mRNA medicines.

Nadolazi cunami mRNA lekova.

Last year, Moderna and AstraZeneca reported positive results

Prošle godine, Moderna i Astrazeneka dobili su pozitivne rezultate

from a clinical trial where patients during open heart surgery

u kliničkom ispitivanju kod operacija na otvorenom srcu

were dosed with messenger RNA injected directly into their heart muscles,

gde su pacijenti dobili dozu informacione RNK direktno u srčane mišiće

that told their heart muscles to grow new blood vessels

koja je govorila srčanim mišićima da stvore nove krvne sudove

in order to get around clogged arteries.

kako bi se zaobišle začepljene arterije.

In other clinical trials we're repeatedly dosing patients

U drugim kliničkim ispitivanjima konstantno doziramo pacijente

with inborn metabolic errors

sa urođenim metaboličkim manama

to treat their metabolic disease.

da bi lečili njihov metabolički poremećaj.

In fact, one of those clinical trials that's currently recruiting patients

Štaviše, jedno od ispitivanja kojima su trenutno potrebni ispitanici

is for von Gierke's disease.

je za lečenje von Girkeove bolesti.

And for cancer patients, we're creating personalized cancer vaccines.

I za pacijente sa rakom, pravimo individulne vakcine protiv raka.

These vaccines are meant to train their bodies,

Te vakcine su namenjene da obučavaju njihova tela

their immune systems, to attack their cancers.

i njihov imunitet da napada kancere.

These are truly personalized medicines, one vaccine for one person.

To su vrlo specifični lekovi, jedna vakcina za samo jednu osobu.

Now for personalized cancer vaccines to be the most effective,

Da bi personalizovane vakcine za kancer bile najučinkovitije,

we need to get them made and back to the patient as quickly as possible.

moramo ih napraviti i dati pacijentu što je pre moguće.

We aim for a turnaround time of 45 days.

Cilj nam je rok od 45 dana.

By January of 2020,

Do januara 2020,

we had already manufactured, quality-controlled and delivered

već smo proizveli, izvršili kontrolu kvaliteta i dostavili

to several dozen patients personalized cancer vaccines.

za više desetina pacijenata individualne vakcine za kancer.

So we had the know-how and the capacity

Imali smo znanje i kapacitet

to manufacture vaccines quickly.

da proizvedemo te vakcine brzo.

Thus, when the sequence of the SARS-CoV-2 virus

I onda kada je sekvenca SARS-CoV-2 virusa

was posted to a public web server on January 10, 2020,

objavljena na javnom veb-serveru 10. januara 2020,

we got immediately to work.

odmah smo se bacili na posao.

Within two days, we had agreed with our collaborators at NIH

U roku od dva dana smo se dogovorili sa našim saradnicima u NIH-u

on exactly which form of the spike protein to put in our vaccine.

koji tip peplomera ćemo staviti u našu vakcinu.

Because we had done so so many times before,

Pošto smo mnogo puta već ovo radili,

it then took our mRNA design team

našem mRNA dizajnerskom timu je bilo potrebno

just one hour to design the mRNA

samo jedan sat da dizajnira mRNA -

that we immediately --

(Applause)

(Aplauz)

That we immediately put on to our manufacturing equipment.

Koju smo odmah stavili na našu opremu za proizvodnju.

We were then able to make that RNA,

Onda smo uspeli da proizvedemo tu RNK,

get it quality-controlled,

da uradimo kontrolu kvaliteta,

fill-finished and shipped off to NIH for the clinical trial in 45 days.

dovršimo i isporučimo Institutima za zdravlje

radi kliničkih ispitivanja sve u roku od 45 dana.

Now what I find --

(Aplauz)

(Applause)

What I find truly remarkable is that that mRNA sequence

Nešto što je po mom mišljenju izuzetno jeste da mRNA sekvenca

that took us one hour to design

za koju je bilo potrebno samo sat vremena da se napravi

is the same mRNA sequence that went into your arms,

je ista mRNA sekvenca koja je išla u vaša ramena,

that ended up in Spikevax, our now fully approved vaccine.

koja je završila u spajkvaksu, našoj sad potpuno odobrenoj vakcini.

One hour to design a medicine that has saved countless lives.

Jedan sat da se dizajnira lek koji je spasio mnogobrojne živote.

(Applause)

(Aplauz)

It still gives me goosebumps every time I talk about it.

I dalje se ježim kada pričam o tome.

So what does the future hold?

Šta sledi u budućnosti?

Well, I've already told you about regenerative medicine

Već sam vam govorila o regenerativnom lečenju

and personalized cancer vaccines.

i personalizovanim vakcinama za kancer.

For cancer patients, we can send in -- by directly injecting

Za pacijente sa rakom, možemo direktno ubrizgati

messenger RNA into their tumors --

informacionu RNK u njihove tumore.

we can send in instructions telling the tumor cells to self-destruct,

Možemo poslati instrukcije ćelijama tumora da se samounište.

Or having the tumor cells send out signals to the immune system,

Ili da ćelije tumora pošalju signal imunom sistemu

beckoning the immune system to attack.

da ih napadne.

For patients with autoimmune disorders,

Za pacijente sa autoimunim bolestima,

we can send in signals that tamp down their overactive immune systems.

možemo poslati signale koji će usporiti njihove preaktivne imune sisteme.

And we and others are rapidly making many more messenger RNA vaccines.

I mi i ostali ubrzano pravimo još mnogo mRNA vakcina.

Because messenger RNA vaccines can be produced so quickly and rapidly,

Pošto se mRNA vakcine mogu brzo proizvoditi,

they're really well suited for newly emerging diseases

one su idealne za novonastale bolesti

as well as other viruses, like the flu,

kao i za ostale viruse, poput gripa,

where new variants come out every year, and the vaccines need to be updated.

gde nove varijante izlaze svake godine i vakcine se moraju prilagođavati.

But one of the exciting things about mRNA medicines

Jedna od najuzbudljivijih stvari kod mRNA vakcina

is we're not limited to sending in the instructions

jeste da nismo ograničeni na slanje instrukcija

for one protein at a time.

za jedan protein pojedinačno.

mRNA medicines can be easily multiplexed.

mRNA lekovi se lako mogu kombinovati.

Therefore, we're working on a combination vaccine

Već radimo na kombinovanoj vakcini

for COVID, flu

za kovid, grip,

and respiratory syncytial virus, or RSV:

i za respiratorni sincicijalni virus ili RSV,

all leading causes of hospitalization and death in the elderly.

koji su glavni uzroci hospitalizacije i smrti starijih osoba.

And we're hoping that this will then be an annual booster,

I nadamo se da će to biti godišnji buster,

that you will get, just like the flu vaccine.

koji ćete dobijati, baš kao vakcinu protiv gripa.

(Applause)

(Aplauz)

So finally, the very modest footprint

I na kraju, skromna oprema

of the manufacturing equipment

for making messenger RNAs

za proizvodnju informacione RNK

means that they can be made almost anywhere in the world.

znači da se ona može proizvoditi skoro bilo gde na svetu.

And to take this to an extreme,

I da dovedemo to do ekstrema,

the American Defense Department started a program in 2019,

Američko ministarstvo odbrane je započelo program 2019,

and we're working with them to miniaturize the entire process

i radimo sa njima da smanjimo čitav proces

so that it can be fit into a single shipping container

tako da može stati u jedan kontejner

for rapid deployment anywhere in the world.

za brzo raspoređivanje bilo gde na svetu.

So --

(Applause)

(Aplauz)

So to finish, I hope I've convinced you

I na kraju, nadam se da sam vas nagovorila

that we have entered an entirely new era of medicine.

da smo ušli u potpuno novu eru medicine.

Having learned to speak the language of mRNA, the language of life,

Kako smo naučili da govorimo jezik mRNA, jezik života,

we can now use it to create medicines that are just for one person,

možemo ga koristiti da pravimo lekove koji mogu biti samo za jednu osobu,

like a personalized cancer vaccine,

poput personalizovane vakcine za kancer,

or can be rapidly produced and distributed to entire populations,

ili za lekove koje možemo ubrzano da proizvedemo i distribuiramo globalno,

like the COVID-19 vaccines.

poput kovid-19 vakcine.

And the best part?

A najbolji deo?

The best part is we're simply tapping into your body's own ability

Najbolji deo je da koristimo sposobnost vašeg tela

to make its own medicines.

da proizvodi sopstvene lekove.

Thank you.

Hvala vam.

(Applause)

(Aplauz)