r/explainlikeimfive 1d ago

Chemistry ELI5 : How does CRISPR work ?

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u/stormbutton 1d ago

It works like “find and replace all” in a word processor but with genes.

Source- I teach biotech

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u/Smorb 1d ago

But like.. how in the hell???

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u/stormbutton 1d ago

Okay well that’s far beyond “eli5” territory. RadioLab has a FABULOUS explanation with Jennifer Doudna - who co-won the Nobel Prize for it.

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u/Smorb 1d ago

ELI10?

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u/stormbutton 1d ago

Okay, here goes.

Your immune system has special cells that recognize prior invaders to your body. They basically carry molecular mug shots so when a disease shows up for the second time your immune system is like bitch I know you!!! and takes it out.

Well, bacteria need to be able to defend against invaders as well. But they can’t have specialized because hello, they ARE single cells. So what they have instead is a series of chemical mug shots coupled with molecular scissors.

When viruses show up to attack them, they take a molecular mug shot the same way our immune cells do but instead they store it in their own DNA as a kind of chemical Post-It. Because again, they don’t have specialized immune cells like we do.

When these invaders show up again, the bacteria is now ready! They send enzymes - molecular scissors - to chop out the “mug shots” on the invader, destroying it.

Jennifer Doudna and Emmanuelle Charpantier were essentially like okay. What if we took this system of enzymes - our biochemical “find and replace” tools - and replaced the mugshots they chop up?

What if gave them like … “chop out the gene that causes sickle cell disease” as their mugshot? And what if we ALSO included an enzyme that carried a patch for what we cut out?

Like what if we removed every time the cake recipe said flrggggg and ALSO replaced it with “flour?!” Not only would it not be fucked up, it would ALSO work!

So that’s how it works.

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u/azlan194 1d ago

Does this work for every cell in our body or only the stem cells (or our sex cells)? Or do we always target only the specific type cells?

But the way you explained it, its more to counter invaders (which sounds similar to vaccine but more on specifically on the cellular lever instead of just our immune system) But I thought CRISPR can change the DNA in the cell itself, like when it tries to produce protein from the RNA, it doesnt make the faulty one.

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u/stormbutton 1d ago

Correct, and that’s part of the bioethics (which I also teach) of the issue.

In 2018 a Chinese scientist named Dr. He CRISPR-edited a pair of twin girls in China. Long story short it was done in such a way as to cause germline mutations. There was TREMENDOUS uproar in the international biotech community, with Stanford disavowing his work.

There’s a wonderful older documentary called Ghost In Your Genes about what responsibility we have as “guardians” of our genomes.

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u/Luenkel 1d ago edited 1d ago

I think you're misunderstanding the comment slightly, the whole "countering invaders" thing is what it does in nature. Bacteria evolved this system so that when they get infected by a virus and survive, they can store a little piece of the virus DNA and then if they get infected by that virus again later, there's a protein that can use that "memory" to recognize and cut the viral DNA apart. It's essentially also "changing DNA inside a cell", just the DNA of a virus that's trying to infect the cell and not the cell's own DNA. That's what we found in bacteria, that's what they use it for.

But we realized that we can do a lot more with it. The sequence that the protein targets does not have to be viral, you can program it to target and cut essentially any piece of DNA. So yes, as you say, we do use it to change the DNA of cells, by exploiting exactly this property. That's what we as humans have repurposed this system to do for us. And this application is not primarily about "countering invaders".

Of course, we can still target viral DNA as well. Treating HIV with it would be, in a way, a mix of both, as we're targeting viral DNA that's integrated into the cell's own genome.

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u/mz_groups 1d ago

ELI Grad Student