How CRISPR lets you edit DNA - Andrea M. Henle

Prevodilac: Aleksandar Bošnjak Lektor: Ivana Krivokuća

From the smallest single-celled organism

Od najmanjeg jednoćelijskog organizma

to the largest creatures on earth,

do najvećih stvorenja na Zemlji,

every living thing is defined by its genes.

svako živo biće definisano je svojim genima.

The DNA contained in our genes acts like an instruction manual for our cells.

DNK koja se nalazi u našim genima deluje kao uputstvo za upotrebu našim ćelijama.

Four building blocks called bases are strung together in precise sequences,

Četiri gradivna bloka zvani baze su postavljeni zajedno u precizne nizove,

which tell the cell how to behave

koji govore ćeliji kako da se ponaša

and form the basis for our every trait.

i formiraju osnovu za svaku našu osobinu.

But with recent advancements in gene editing tools,

Sa skorašnjim naprecima alatki za uređivanje gena,

scientists can change an organism’s fundamental features in record time.

naučnici mogu izmeniti osnovne odlike organizma u rekordnom vremenu.

They can engineer drought-resistant crops

Mogu genetski modifikovati da usevi budu otporni na sušu

and create apples that don’t brown.

i da stvore jabuke koje ne postaju braon.

They might even prevent the spread of infectious outbreaks

Možda čak i spreče širenje infektivnih bolesti

and develop cures for genetic diseases.

i razviju lekove za genetske bolesti.

CRISPR is the fastest, easiest, and cheapest of the gene editing tools

Krispr je najbrža, najlakša i najjeftinija alatka za uređivanje gena

responsible for this new wave of science.

koja je odgovorna za ovaj novi talas nauke.

But where did this medical marvel come from?

Nego, odakle se ovo medicinsko čudo pojavilo?

How does it work?

Kako funkcioniše?

And what can it do?

I šta može da uradi?

Surprisingly, CRISPR is actually a natural process

Iznenađujuće, Krispr je zapravo prirodan proces

that’s long functioned as a bacterial immune system.

koji je dugo funkcionisao kao bakterijski imuni sistem.

Originally found defending single-celled bacteria and archaea

Prvobitno nađen kako brani jednoćelijske bakterije i arheje

against invading viruses,

od virusa koji napadaju,

naturally occurring CRISPR uses two main components.

prirodni Krispr koristi dve glavne komponente.

The first are short snippets of repetitive DNA sequences

Prva su kratki isečci DNK nizova koji se ponavljaju

called “clustered regularly interspaced short palindromic repeats,”

i zovu se „pravilno razmaknuta grupisana kratka palindromska ponavljanja”,

or simply, CRISPRs.

ili jednostavno Krispr.

The second are Cas,

Druga komponenta su kas proteini,

or “CRISPR-associated” proteins

ili proteini udruženi sa Krisprom

which chop up DNA like molecular scissors.

koji seckaju DNK kao molekularne makaze.

When a virus invades a bacterium,

Kada virus napadne bakteriju,

Cas proteins cut out a segment of the viral DNA

kas proteini odsecaju segment virusne DNK

to stitch into the bacterium’s CRISPR region,

i ubacuju ga u deo bakterije gde je Krispr,

capturing a chemical snapshot of the infection.

pamteći hemijski snimak infekcije.

Those viral codes are then copied into short pieces of RNA.

Ti virusni kodovi se onda kopiraju u kratke delove RNK.

This molecule plays many roles in our cells,

Ovaj molekul ima više uloga u našim ćelijama,

but in the case of CRISPR,

ali u slučaju Krispra,

RNA binds to a special protein called Cas9.

RNK se vezuje za specijalni protein koji se naziva kas 9.

The resulting complexes act like scouts,

Dobijene celine se ponašaju kao izviđači

latching onto free-floating genetic material

koji se vezuju za genetski materijal koji slobodno pluta

and searching for a match to the virus.

i traže spoj koji odgovara virusu.

If the virus invades again, the scout complex recognizes it immediately,

Ako virus ponovo napadne, izviđačka celina ga odmah prepoznaje

and Cas9 swiftly destroys the viral DNA.

i kas 9 brzo uništava virusnu DNK.

Lots of bacteria have this type of defense mechanism.

Mnogo bakterija ima ovaj tip odbrambenog sistema.

But in 2012, scientists figured out how to hijack CRISPR

Ali 2012. godine naučnici su otkrili kako da nasamare Krispr

to target not just viral DNA,

da cilja ne samo virusnu DNK,

but any DNA in almost any organism.

nego bilo koju DNK u skoro bilo kom organizmu.

With the right tools,

Sa pravim alatkama,

this viral immune system becomes a precise gene-editing tool,

ovaj virusni imuni sistem postaje precizna alatka za uređivanje gena,

which can alter DNA and change specific genes

koja može da izmeni DNK i promeni određene gene

almost as easily as fixing a typo.

lako kao da ispravlja slovnu grešku.

Here’s how it works in the lab:

Evo kako funkcioniše u laboratoriji:

scientists design a “guide” RNA to match the gene they want to edit,

naučnici dizajniraju RNK „vodiča” tako da odgovara genu koji žele da izmene,

and attach it to Cas9.

i vezuju ga za kas 9.

Like the viral RNA in the CRISPR immune system,

Kao virusna RNK u imunom sistemu Krispra,

the guide RNA directs Cas9 to the target gene,

RNK vodič usmerava kas 9 do ciljanog gena,

and the protein’s molecular scissors snip the DNA.

i proteinove molekularne makaze odrezuju DNK.

This is the key to CRISPR’s power:

To je ključ Krisprove moći:

just by injecting Cas9 bound to a short piece of custom guide RNA

samim ubrizgavanjem kas 9 proteina vezanog za kratki deo prilagođenog RNK vodiča,

scientists can edit practically any gene in the genome.

naučnici mogu da izmene skoro bilo koji gen u genomu.

Once the DNA is cut,

Kad je DNK isečena,

the cell will try to repair it.

ćelija će pokušati da je popravi.

Typically, proteins called nucleases

Obično, proteini zvani nukleaze

trim the broken ends and join them back together.

dovode u red oštećene krajeve i spajaju ih ponovo.

But this type of repair process,

Ali ovaj tip procesa popravke,

called nonhomologous end joining,

zvan spajanje nehomologih krajeva,

is prone to mistakes

je sklon greškama

and can lead to extra or missing bases.

i može dovesti do dodatnih ili izgubljenih baza.

The resulting gene is often unusable and turned off.

Dobijeni gen je često neupotrebljiv i ugašen.

However, if scientists add a separate sequence of template DNA

Međutim, ako naučnici dodaju odvojeni niz šablonske DNK

to their CRISPR cocktail,

svom koktelu Krispra,

cellular proteins can perform a different DNA repair process,

ćelijski proteini mogu da izvrše drugačiji proces popravke DNK,

called homology directed repair.

zvan popravka usmerena na homologiju.

This template DNA is used as a blueprint to guide the rebuilding process,

Ovaj šablon DNK je korišćen kao plan za rukovođenje procesom ponovne izgradnje

repairing a defective gene

kojim se popravlja neispravan gen

or even inserting a completely new one.

ili čak ubacuje potpuno novi.

The ability to fix DNA errors

Sposobnost da popravlja greške DNK

means that CRISPR could potentially create new treatments for diseases

znači da bi Krispr potencijalno mogao da stvori nove lekove za bolesti

linked to specific genetic errors, like cystic fibrosis or sickle cell anemia.

u vezi sa specifičnim genetskim greškama, poput cistične fibroze i srpaste anemije.

And since it’s not limited to humans,

Budući da nije ograničen samo na ljude,

the applications are almost endless.

upotrebe su skoro beskrajne.

CRISPR could create plants that yield larger fruit,

Krispr bi mogao da stvori biljke koje rađaju veće voće,

mosquitoes that can’t transmit malaria,

komarce koji ne mogu da prenesu malariju,

or even reprogram drug-resistant cancer cells.

ili čak da reprogramira ćelije raka koje su otporne na lekove.

It’s also a powerful tool for studying the genome,

Takođe je moćna alatka za proučavanje genoma,

allowing scientists to watch what happens when genes are turned off

koja dopušta naučnicima da gledaju šta se dešava kad su geni ugašeni

or changed within an organism.

ili promenjeni unutar organizma.

CRISPR isn’t perfect yet.

Krispr još nije usavršen.

It doesn’t always make just the intended changes,

Ne pravi uvek samo zamišljene promene,

and since it’s difficult to predict the long-term implications of a CRISPR edit,

i budući da je teško predvideti dugoročne posledice uređivanja Krisprom,

this technology raises big ethical questions.

ova tehnologija postavlja značajna etička pitanja.

It’s up to us to decide the best course forward

Na nama je da odlučimo o najboljem pravcu

as CRISPR leaves single-celled organisms behind

dok Krispr ostavlja jednoćelijske organizme iza sebe

and heads into labs, farms, hospitals,

i upućuje se u laboratorije, farme, bolnice

and organisms around the world.

i organizme širom sveta.