
Super-precise new CRISPR tool could tackle a plethora of genetic diseases - Reedx
https://www.nature.com/articles/d41586-019-03164-5
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aaavl2821
This seems like really cool tech but it is always important to be aware of
hype. For a take on the limitations of the paper from a postdoc in another MIT
lab:
[https://twitter.com/circuit_logic/status/1186644783751544832](https://twitter.com/circuit_logic/status/1186644783751544832)

The tech has already been licensed to a new company backed by top biotech VCs
ARCH, GV, F-Prime and Newpath

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ChuckMcM
This is a good advancement on CRISPR, it gets us one step closer to having
treatments for disease that is genetically linked. It also gets us one step
closer to having a 'genome debugger' which would be a tool for analyzing what
every gene does in isolation so that the effect of changes can be more
accurately modeled (and predicted).

The scary part of that for me is that we get closer to having genomic 'zero
days' where an underground lab has figured out how to create a pathogen that
has a specific (and negative) targeted effect on a particular gene or gene
group. Such a tool in the hands of someone who is looking to do some "ethnic
cleansing" is a concern for me.

~~~
Klinky
We already have nukes, and you can still do ethnic cleansing most cheaply with
conventional weapons and impotent nation states, no need for Super CRISPR.

~~~
jacquesm
Nukes have signatures. This does not. Just a little aerosol in your general
vicinity would likely do the job and you'd never be the wiser. Besides that it
is orders of magnitude easier and cheaper to do this than build a nuke once
you can mail order for genetic sequences delivered to your door.

~~~
zaarn
The Problems with Bioweapons (and you need bio here, either a bacteria or
virus that delivers the crispr genedrive, a single spray won't be enough), is
that they evolve.

Your super virus that you developed to only kill people living in southern
florida? Yeah, that now developed to also kill people in new york. And now
it's the whole world.

~~~
jacquesm
That's not how it works.

It would work like this: you'd design a bioweapon to hit the Jewish people
exclusively (they're the punchball of history, forgive me using them again as
an example but I think it is a likely occurrence if this sort of thing is to
happen). Then it will may evolve to hit others.

~~~
zaarn
I purposely didn't select any specific ethnicity or other genetic factor to
avoid tapping into stereotypes or causing offence (except to people living in
Florida, sorry but not sorry).

~~~
jacquesm
Genetic weapons will use genetic factors.

~~~
zaarn
Correct but nobody has proved that new yorkers don't have a common mutation
that forces them to live in that city.

~~~
jacquesm
You don't need to prove nonsense. You also can't prove the absence of
nonsense.

~~~
zaarn
Correct, but I can substitute potentially offensive or offputting labels with
nonsense to get a point across.

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WaitWaitWha
recently, seems, many, a lot of, very, completely, appears, most, far more
likely, huge, could, some, may...

so that's

-13 for weaseling

+1 doi link provided

+1 doi points to the actual article

~~~
dpq
For the better or worse, this is the standard language for modern academic
writing. Do not blame the authors if this social convention is not to your
liking.

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dandare
I understand that CRISPR can change the genome in a specific chromosome, but
how do you change the genome in all cells of a body? Or you don't need to
change all cells in order to cure genetic disease?

~~~
SuoDuanDao
It's difficult. The standard way in frogs is to just keep injecting them until
the altered cells outnumber the regular ones. You wouldn't have to change them
all though, often genetic diseases are confined to a particular tissue.

There are also theories around using a live virus to carry the genetic
material, theoretically a virus like that could leave behind the desired
mutation as it replicates through the body's cells. Promising mechanism,
though I don't know of anyone who's pulled it off.

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foobarbecue
Prime editing is not CRISPR or "a CRISPR tool." It's an alternative to CRISPR.

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EGreg
Does CRISPR work on all cells at once? Or we are talking about gametes?

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aaavl2821
It does not work on all cells at once. For a cell's genes to be edited, the
cell must receive its own copy of CRISPR-Cas9 or whatever other gene editing
system.

Delivery of gene editing systems to the right cells is a major challenge. At
present, most gene editing therapies involve:

* extracting blood cells from a patient, editing them ex vivo, optionally selecting for successfully edited cells, and readministering to patients

* delivering gene therapy with viral vectors and treating diseases where you don't need to edit 100% of relevant cells for the treatment to be effective, and targeting cells that are easier for the viral vectors to infect (typically motor neurons, the eye, blood cells or the liver)

It isn't really possible to edit every or most cells in the body with current
technology. It is possible to edit gametes but it is not currently ethical to
do so as we don't understand the risks and the potential for abuse is huge

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inciampati
The key advance in this work is showing a way to edit without any external
inputs to the cell (in the form of DNA templates). This suggests the
possibility of in cell feedback systems. I don't get the best vibe from all
the rush to market and focus on correcting generic disorders. Is that really
what gene editing is for?

~~~
aaavl2821
I'm not an expert but I believe that one of the key advances here is that this
technology can introduce new DNA via more precise mechanisms, breaking just
one DNA strand at a time.

Current CRISPR tech involves "double stranded breaks": cutting both strands of
DNA. The body has a few ways of dealing with and repairing these breaks, one
of which scientists can use to insert new DNA of their choosing [0]. However
in other cases the cell uses a different repair pathway that can introduce
mutations (including insertions or deletions of DNA). These mutations can be
harmful especially if for example they mutate a tumor suppressor gene

The new approach here apparently has less of a risk of introducing these
mutations bc it does not cause double strand breaks, so does not trigger
potentially erroneous repairs that cause harmful mutations

But I'm not an expert so if this is incorrect or if I'm missing something
please chime in

[0] [https://blog.addgene.org/crispr-101-homology-directed-
repair](https://blog.addgene.org/crispr-101-homology-directed-repair)

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chrisco255
What are the biggest risks with CRISPR? Seems like a double edged sword to me.

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ebg13
> _What are the biggest risks with CRISPR?_

So far, that using it causes cancer.

~~~
vikramkr
I don't recall a clear causal link being drawn beyond some favoring off cells
with inhibitions in apoptotic pathways being more likely to successfully
undergo crispr knockout- certainly a risk but nothing like what you're
suggesting with that strong statement. Can you elaborate on your point? I'd
love to learn if there was any more research into that, it's an important
question for sure.

~~~
aaavl2821
Here's fairly approachable summary of some of the risks:
[https://www.synthego.com/blog/crispr-cancer-research-
studies](https://www.synthego.com/blog/crispr-cancer-research-studies)

This discusses a few papers showing that CRISRP-Cas9 can cause "off target"
mutations in a tumor suppressor gene called p53. If these mutations render p53
non functional it is possible that these cells can become cancerous

That is one of the specific risks identified although there are in theory
other risks

~~~
vikramkr
I dont think the cas9 is causing the off target mutations according to those
papers, it's more potentially selecting for cells with already dysfunctional
p53 in those few cell lines by inducing a p53 mediated dna damage response.
It's in cells that arent going to go near humans and are pretty different in
form and function than those used in trials, and while it's a risk to consider
(not trying to downplay potential risks here- all new medicine and biology
must be thoroughly evaluated for safety and risk), it's nowhere near a show-
stopping demonstration that CAS9 mediated editing causes cancer and hasn't
stopped clinical trials from moving forward

~~~
aaavl2821
Thanks for the correction, I was thinking of potential for off target edits
that lead to cancer but you are right, that's the wrong article for discussion
of off target

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oarabbus_
I think it's worth pointing out that this headline pops up every time there's
a minor improvement to CRISPR/casX regardless of whether it's a substantial
improvement or not.

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rpmisms
CRISPR is a bit of a catch-all term, and "could tackle a plethora of genetic
diseases" is not informative.

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bryanrasmussen
I uhm, posted this a while ago
[https://news.ycombinator.com/item?id=21315326](https://news.ycombinator.com/item?id=21315326)

on edit: but I guess it's been a while.

~~~
dang
Reposts are fine if a story hasn't had significant attention yet:
[https://news.ycombinator.com/newsfaq.html](https://news.ycombinator.com/newsfaq.html).
On HN we try to give good stories multiple cracks at the bat.

Eventually we want to implement a karma-sharing system so earlier submitters
benefit from reposts that catch on. In the meantime, it's a bit of a
lottery—but if you submit enough good stories it evens out over time.

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markdown
Why do people even share this sort of news anymore. I don't think I've
___ever_ __read an article about novel medical science that is supposed to
treat [bad disease] that eventuated in any actual treatment or cure.

The actual cure is perpetually a decade away.

~~~
Majestic121
That's because the process to put a novel technology on the market takes
approximately 10 years. Clinical trials are long, but new tech do get there

~~~
markdown
You didn't answer my question. Yes, of course clinical trials take forever.
Why share this article here or anywhere? There is no cure or treatment for
anything mentioned in the article. There might be one, but if there is it's a
decade away. How is that news?

It's like someone writing an article about a few people potentially being
President of the USA a decade from now. Except nobody is actually named in the
article. Would you share such an article?

Is there a lot of money invested in CRISPR? Is this all about building hype
for CRISPR? Because I can't think of another motive.

~~~
jfarlow
It's also a lot like an announcement of any other tool of great importance: a
new programming language, a new rocket engine, a new alloy, a new
psychological principle - or any other discovery of import. It's profoundly
interesting to watch, understand, and organize those discoveries (as news) -
precisely so the more pragmatic downstream affects can be achieved.

Those who can put those various discoveries together are those that will be
the ones that use those tools in conjunction in order to benefit everyone. But
how are they to know about them if the discoveries themselves 'are not news'?

