How hard would it be to attack coronavirus with CRISPR?

post by Donald Hobson (donald-hobson) · 2020-03-06T23:18:09.133Z · LW · GW · No comments

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    11 johnswentworth
    2 brianwang712
    -9 jimrandomh
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Crisper can snip genomes in particular spots, we probably have the genome of corona virus. Viruses probably don't work if their genome is chopped up. What would happen if you loaded random chunks of the coronavirus genome into crispr, and injected it into someone with coronavirus? I don't know much biology, this may be completely stupid, but if there is someone out their with enough biology knowledge and biohacking skills...

EDIT:

Virus DNA is wrapped in protien shells in the intercellular fluid. You need some way to get your CAS9 into cells, like wrapping it in a virus protien shell, to hijack the viral delivery mechanism. We can use coronavirus itself. Get cas9 targeted to the coronavirus genome, put it within a coronavirus protien shell, and inhale the spray. (You don't need the defences in all your cells, just in your lungs.) The virus injects cas9 in to your cells, if you don't get coronavirus, the cas9 does nothing. If you get it in a cell, the cas9 chops it up. The virus protien shells help train your immune system.

EDIT2

Mutation rate, most of the time, one snip will kill it, sometimes it could mutate. Don't set the crispr to a part you don't want to mutate. Set it somewhere where mutations are harmful in the coronavirus genome, do these viruses have a part that looks the same?

Answers

answer by johnswentworth · 2020-03-07T00:12:27.123Z · LW(p) · GW(p)

This is actually pretty similar to the original function of the CRISPR/CAS9 system in the wild. Wild bacterial CRISPR systems copy short RNA segments complementary to bacteriophage DNA, then use those to target and destroy any phage DNA within the bacteria. So it's definitely something which could work in principle, and is already used by some bacteria.

That said, at this point it would probably be harder to immunize against a virus using CRISPR-based techniques than using traditional vaccines. Just injecting a bunch of CRISPR protein machinery and bits of coronavirus-complementary RNA directly into the bloodstream wouldn't really do anything; you'd need to genetically modify human cells to produce the CRISPR machinery themselves.

(Side note: you might be interested in Todd Rider's DRACO project.)

answer by brianwang712 · 2020-03-15T19:20:34.737Z · LW(p) · GW(p)

It was only a matter of time before somebody tried this: https://www.biorxiv.org/content/10.1101/2020.03.13.991307v1.full.pdf

From the abstract: "Here we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), for viral inhibition that can effectively degrade SARS-CoV-2 sequences and live influenza A virus (IAV) genome in human lung epithelial cells. We designed and screened a group of CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs for cleaving SARSCoV-2...The PAC-MAN approach is potentially a rapidly implementable pan-coronavirus strategy to deal with emerging pandemic strains. "

answer by jimrandomh · 2020-03-06T23:58:43.248Z · LW(p) · GW(p)

This won't work, and is nowhere close to the sort of thing that could work. In order to work as an antiviral, a drug has to selectively kill viruses without also damaging uninfected lung cells. CRISPR is not able to target viruses at all, and also does not destroy the things it targets.

↑ comment by brianwang712 · 2020-03-07T13:50:17.213Z · LW(p) · GW(p)

I downvoted this comment (as well as your comment below) for strongly pushing misinformation. As others have noted, the CRISPR/Cas9 system has evolved in bacteria precisely to target viral genomes — "CRISPR is not able to target viruses at all" is simply false. "...and also does not destroy the things it targets" is also false, in a sense; a well-targeted Cas9-induced double-stranded break in the DNA/RNA of a viral genome can certainly disable a crucial viral gene and reduce viral replication, even if you don't consider this "destruction" of the genome.

That's not to say that the CRISPR/Cas9 system is quite ready for antiviral therapy in vivo. One problem is that you could rapidly generate viral escape mutants. Not only do you create selection pressure for the virus to mutate such that your bespoke CRISPR/Cas9 system can't target it anymore, the Cas9 cutting itself guides this process along more rapidly, since double-stranded breaks are often accompanied by random insertions and deletions at the cut site (incorporated during attempted cellular repair of the break). This could potentially be addressed by targeting important, conserved regions of the viral genome and/or by multiplexed editing (i.e., targeting multiple sites simultaneously).

Perhaps a bigger challenge is delivery. Systemic delivery (i.e., throughout the body) is risky, since you can get off-target edits in cells that aren't even infected with virus, which could result in increased risk of cancer or other maladies. Targeted delivery to only a certain class of cells of interest is sometimes possible but difficult. There's also the perennial question of whether or not your looks-good-on-paper molecular mechanism of action translates to real clinical benefits, something that can only really be definitively answered in clinical trials. For example, you might see efficient viral genome cutting in vitro but see no clinical benefit in a patient, because maybe your Cas9 protein doesn't stick around long enough in cells, or maybe you can't get it into enough cells to matter, or it's detrimentally immunogenic, or a host of other hard-to-evaluate-in-advance reasons.

All that being said, this is a real direction of interest and many are looking into it — the OP is not "completely on the wrong track" and this idea is not "nowhere close to the sort of thing that would work". The fact that CRISPR/Cas9 is so programmable makes its potential use as an antiviral therapy exciting and at least worth exploring more, in my view. Here's a nice review if anyone would like to learn more (warning: paywalled): https://www.cell.com/trends/microbiology/fulltext/S0966-842X(17)30093-8

Replies from: donald-hobson
↑ comment by Donald Hobson (donald-hobson) · 2020-03-07T00:09:14.326Z · LW(p) · GW(p)

cas9 can be set to target arbitrary DNA sequences, it is part of a bacterial virus defence mechanism. If you have your cas9, in a cell, and then a virus tries to infect it, the viral genome will get chopped up. I don't think viral DNA works when chopped up, especially as the researchers can cut somewhere that will do lots of damage, like in the middle of a gene that makes a key protein.

This is assuming that you can get cas9 into cells.

Replies from: jimrandomh
↑ comment by jimrandomh · 2020-03-07T00:22:46.362Z · LW(p) · GW(p)

"Does damage to DNA" is not a feature that distinguishes CAS9 from bleach. Also, coronavirus does not contain DNA; it's an RNA virus. You're completely on the wrong track.

Replies from: donald-hobson

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