
Very fast CRISPR on demand - XzetaU8
https://science.sciencemag.org/content/368/6496/1265
======
jcims
Will be interesting to see how ML and CRISPR converge. Two systems we don't
fully understand creating explicit capability we desire and latent capability
we don't expect.

I'm curious if there will eventually be some kind of biological incarnation of
cellular automata that is useful for chemical synthesis or material
fabrication. Clearly we have that with individual organisms now (e.g. insulin
manufacture) but imagine seeding a matrix with bacteria that extrude carbon
nanotubes under UV light or similar oddities.

~~~
hobofan
> Will be interesting to see how ML and CRISPR converge

I've been seeing similar comments a lot lately, and I don't understand why. As
someone with a background in ML that is now studying biochemistry I'd be the
first person to jump at something like that, but I'm just not seeing any big
ML potential that directly has to do with CRISPR.

Is it just two hyped technologies being thrown in a pot? Is there something
I'm missing?

~~~
nisten
I know you what you're missing. You gotta put AI in the Blockchain before
adding CRISPER and applying for funding.

EDIT: And don't forget Kubernetes.

~~~
choeger
Serverless Gene editing!

~~~
nisten
CRISPRAAS

~~~
jcims
You laugh but...

[https://www.genscript.com/crispr-
services.html](https://www.genscript.com/crispr-services.html)

[https://canopybiosciences.com/custom-cell-line-
engineering-2...](https://canopybiosciences.com/custom-cell-line-
engineering-2/)

[https://www.reprocell.com/gene-editing-
services-i174](https://www.reprocell.com/gene-editing-services-i174)

etc. etc.

This guy lifestreams some really interesting work -
[https://www.youtube.com/user/TheChemlife/videos](https://www.youtube.com/user/TheChemlife/videos)

------
amelius
Funny to see sales/marketing lingo in the title of a scientific article, but
with an unexpected meaning.

~~~
jbj
I think they mean "on demand" is that the Cas9 proteins is activated upon
activation of the light source. As the CRISPR/Cas9 complex is already in place
due to the chemically boxed guide RNA, the way I understand it from briefly
skimming this abstract is literally that you turn on the light when you want
DNA cleavage, so I don't see anything weird about it, but maybe someone with
more insight can correct me if I am wrong.

------
tmikaeld
Site is hugged to death already.

Archive snapshot can be found here:
[https://web.archive.org/web/20200616103722/https://science.s...](https://web.archive.org/web/20200616103722/https://science.sciencemag.org/content/368/6496/1265)

------
ishan_kart
Can someone explain?

~~~
flobosg
Here's the Perspective piece on the paper:
[https://science.sciencemag.org/content/368/6496/1180](https://science.sciencemag.org/content/368/6496/1180)

~~~
gavribirnbaum
still don't get it :D for dummies explanation?

~~~
SuoDuanDao
I'm at the limit of my understanding myself, but here's what I think is being
said:

CRISPR refers to the kind of DNA site that can be targeted for cleavage, while
CAS9 is a protein that, paired with an RNA matching that site, can cleave
wherever it encounters a matching sequence.

I think these guys are pairing a variation of the CRISPR approach with a
laser. They pre-bond with the DNA, but the actual cleavage occurs when they
shine a laser at the right frequency at the site. That lets them decide when
and where on the DNA strand cleavage happens.

If anyone understands this better than me, I'd appreciate any corrections to
my explanation ;P

~~~
shpongled
Close - from my quick skim here's my take

The RNA guide (sgRNA) is chemically caged here, so it has some molecular
decorations that are removed with light. The sgRNA can't fully match the
underlying DNA it's recognizing until those decorations have been removed with
the laser, at which point Cas9 then cleaves the DNA strand.

Think of the sgRNA like a regex pattern. Cas9 is like the regex engine here
(but instead of capturing a group, it cuts the sequence), and DNA is the
search space. In this system, we essentially have a full match, and Cas9 is in
position (having found the match) but it can't cleave yet, because the
decorations are blocking the way. As soon as the decorations are removed by
light, the sgRNA can move down into a full match, and Cas9 then cleaves.

~~~
SuoDuanDao
Ah, thank you. So is the benefit of this system that the Cas9 sticks around
for a while, and at any point one can cleave all the sites at once instead of
cleaving each as the Cas9 bumps into it?

~~~
shpongled
Even in standard CRISPR/Cas9 systems, Cas9 sticks around for quite a while -
which is one of the issues in using it for actual medical treatments. You
don't really want a programmable DNA cleavage engine roaming around in your
nucleus...

The primary benefit here is that you can temporally synchronize Cas9. In
standard systems, you introduce Cas9 into the cell, and you have no control
over when it performs cleavage, since it's essentially a greedy cleavage
mechanism - as soon as it finds a match, it cleaves.

This system basically introduces a semaphore, so that you introduce Cas9,
allow it find a match and pause. You can then signal for cleavage to begin. As
stated in the abstract, this is useful for e.g. studying the kinetics of DNA
repair, since you can control when DNA damage (Cas9 cleavage) is happening.

~~~
SuoDuanDao
Fascinating. Thank you so much for taking the time to explain further!

