NHacker Next
  • new
  • past
  • show
  • ask
  • show
  • jobs
  • submit
CRISPR tech selectively shreds cancer cells, including "undruggable" cancers (innovativegenomics.org)
bonsai_spool 2 hours ago [-]
Here's their preprint from a month ago, in case you can't access the Nature paper: https://www.biorxiv.org/content/10.64898/2026.05.08.723607v1

Nature - https://www.nature.com/articles/s41586-026-10738-7

MontyCarloHall 11 minutes ago [-]
The idea of using CRISPR/Cas to detect tumor-specific mutations that aren't necessarily oncogenic and then kill the cell is not a new one [0, 1, 2]. However, previous studies used Cas9, which just damages the DNA at the target site; this uses Cas12a2, which is far more destructive because it shreds the chromatin in the cell once activated by detecting the target sequence.

As with any cancer treatment, it's likely the tumor will evolve resistance. My guess is that cells will find ways to reject the lipid nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide sequence(s), either via modifications to the cell surface (preventing LNP uptake) or via changes to endosomal/lysosomal pathways (causing the mRNA payload to get degraded before it has a chance to be translated into protein).

[0] https://pubmed.ncbi.nlm.nih.gov/28575452/

[1] https://www.nature.com/articles/s41598-018-30205-2

[2] https://www.nature.com/articles/s41467-020-18875-x

AnimalMuppet 2 minutes ago [-]
But cancer isn't an organism. Cancer cells in any specific individual may evolve that way, but "human cancers" as a group will not. (The only way they could is by evolving human DNA, but "survival of the fittest" pushes the opposite direction for that.)
cyberax 4 minutes ago [-]
There are some ideas about making it triggerable. So first you load the cells with a protein that is ready to start shredding but is inactive. Then you trigger it with a second compound.
ordinaryradical 1 hours ago [-]
CRISPR is an extremely overhyped approach which found a marketing engine via popular science. There is 1 FDA approved CRISPR therapy as compared to 7 for AAV and 7 for Lentivirus.

Counting all viral vector therapies that have been approved, we’re sitting at 19 approved therapies versus 1 for CRISPR.

I think CRISPR ideas in a lab are just an easy way into the mainstream press, but viral vector delivery is the real future. It just didn’t get the same news cycle, for whatever reason.

spligak 1 hours ago [-]
You're correct about CRISPR Cas9. The off-target affects are difficult to manage.

The paper describes Cas12a2. This is a different mechanism with discovery origins in - of all things - agriculture. It does not attempt in any way to reprogram cells. It uses a guide protein to locate a specific mutation with exacting precision and, when it activates, unleashes total destruction of the cell.

The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.

Source: I have personally funded novel research based on Cas12a2 for an undruggable condition I have. I have personally seen my condition "cured" in vitro using this technology and it left all of my WT cells unharmed. Some of the researchers I've funded are co-authors in the paper linked. I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.

Gethsemane 34 minutes ago [-]
Have you written about your experience anywhere? It would be interesting to see how you approached the research sector as a layperson. Are there any plans to move to in vivo? Best of luck with your research!
shevy-java 15 minutes ago [-]
So how does Cas12a2 mitigate off-target effects?

If it were to work, gene therapy as-is would be possible. Which it is not, not even for those overpriced therapies. I have no doubt that sooner or later it will happen, as the problem space is finite, not infinite, but I simply don't see the correlation here.

> The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.

So what does this change exactly? Humans defined it as "undruggable conditions". You can reason this is an improvement, but I still see it in failure-territory. If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.

> I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.

How does "answering questions" offset the technology being inferior right now?

GaggiX 57 minutes ago [-]
I know nothing about this field, but I imagine the actual problem is how do you deliver the Cas12a2 protein to each individual cancer cell compare to a viral gene therapy?
spligak 47 minutes ago [-]
There are two major problems, delivery is one of them. Collateral damage of mass cell destruction leading to systemic inflammation is the other.

The approach I'm reviewing now uses lipid nanoparticles (LNPs) for delivery. It isn't great for targeting my bone marrow condition but its workable. The team hasn't optimized it at all, either. There are also viral delivery mechanisms that I haven't studied yet.

The collateral damage problem is the backpressure on the delivery problem. If you get really good at delivery, you can destroy A LOT of cells very quickly. The human body (usually) responds to these events by releasing a lot of pro-inflammatory cytokines. This can lead to cytokine storms or worse.

As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.

shevy-java 11 minutes ago [-]
Lipid nanoparticles are quite old as-is. How do you target cells specifically?

> If you get really good at delivery, you can destroy A LOT of cells very quickly.

You can destroy cells quickly. Ok. So the question is: how do you detect specifically only cancer cells via lipid nanoparticles? That was already a problem years ago with Herceptin. The rationale that is always used is that "we need to do something" for certain aggressive cancers. It has never been a super-effective technique, despite all the promo of how monoclonal antibodies are so accurate.

> As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.

That's already the status quo in the whole cancer field. I don't think that more than sloppy accuracy is acceptable for any gene therapy - and the off-target cleaving of CRISPR has always been the number #1 problem here.

cyberax 1 minutes ago [-]
> So the question is: how do you detect specifically only cancer cells via lipid nanoparticles?

You don't. Healthy cells will also get these nanoparticles, but without the triggering DNA sequence, the mRNA payload will remain inert and eventually will be degraded.

im3w1l 18 minutes ago [-]
Naively, I would deal with this by deciding how many cells I want to kill each day and then figure out a dosing schedule that achieves that. Or maybe it's better to do one dose every few days. But yeah either way.
ramraj07 56 minutes ago [-]
Devils advocate, I also vehemently shat on RNAi therapeutics a decade back. We do have RNAi therapies in market now though. I do think Crispr will find its place similarly.
fastball 1 hours ago [-]
Viral vector delivery is indeed harder to sell with PopSci, what with movies like "I am Legend".
jvanderbot 1 hours ago [-]
Great first half of a movie, by the way. Up there with Sunshine for "Sit down for a great hour-long ambiance".

I usually end Legend after the mannequin trap, and end Sunshine after the transit of mercury.

roncesvalles 58 minutes ago [-]
CRIPSR was a game-changer for genetics research. A lot of gene knockout studies use CRISPR. However, it was always weirdly overhyped for clinical use from the beginning and this was obvious to anyone with a genetics background.

The public in general doesn't have a good understanding of basic genetics and I blame high school science curriculums for not covering it well enough. Too much time is wasted on Mendelian genetics without covering the Central Dogma.

You basically cannot "edit" your somatic DNA in a meaningful wholesale way since every single cell in your body has a copy of the DNA, and it's a foolish endeavor. What you can conceivably edit to good effect is your germline DNA, stem cell DNA, or modify mRNA expression (e.g. retinoids; yes putting retinol/adapalene cream on your face is "gene therapy"), or introduce foreign mRNA for your translation machinery to co-opt (e.g. mRNA vaccines).

projektfu 6 minutes ago [-]
I disagree that it's "gene therapy" to affect the natural regulation of mRNA production. If that were true then the term "gene therapy" loses its meaning, as just about everything changes the expression of mRNA. You can probably do so somewhere just by thinking really hard about it.

Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.

Bjartr 52 minutes ago [-]
Edit every cell? No. Edit enough cells to impact health outcomes for a meaningful period of time? [Yes](https://www.youtube.com/watch?v=J3FcbFqSoQY)
shevy-java 9 minutes ago [-]
This approach can work for some genetic diseases such as blindness based on some cells in the retina or partial blindness. For others this is not really a cure. If you want to cure people with progeria, does curing 20% of the cells really help? Perhaps 100% is not necessary, but it would seem strange to cure only some cells but not others. You'd have a mosaic of cells where some would work and others don't. Cells interact; timing also plays a role in development. I don't really see that aiming for anything but a very high number of cells cured, can work.
perlgeek 51 minutes ago [-]
CRISPR is foremost a research tool. Calling it "extremely overhyped" without restricting it medical treatment seems disingenuous.

The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't find it surprising that merely 14 years later, there's only one approved treatment. From discovery to approval, drug development often takes 10-15 years, and often much longer for novel techniques. So I'd say it too early to call it overhyped for treatments.

Finally, I think we'll see a lot of treatments that don't use CRISPR-Cas9, but related gene editing techniques, but it'll take another 10 to 20 years.

Take a look at https://en.wikipedia.org/wiki/MRNA_vaccine#History for how long another novel technique has been in development before it became really widespread with the mrna-based covid-19 vaccines.

shevy-java 7 minutes ago [-]
Why does it take 20 years? Except, of course, that it does not work nowhere near as well as it is being promoted - aka hyped.

mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.

jagged-chisel 54 minutes ago [-]
“Virus” - that’s why.
anovikov 1 hours ago [-]
Bingo! CRISPR has an advantage of being relatively easy to describe to a layman, giving it a PR advantage.
fragmede 1 hours ago [-]
So is the "idea" of microchips in vaccines. Should we just give up and let everything else have the PR advantage
mondomondo 1 hours ago [-]
[dead]
Ifkaluva 2 hours ago [-]
I hope this finally works out. I remember almost exactly ten years ago I got excited about one of these proposed cancer cures, tried to talk about it at lunch with my coworkers, and they laughed at me for believing.
arcticfox 2 hours ago [-]
I'm pretty optimistic. I think it's a threshold question where we need a number of basic technologies to all get over certain bars before the floodgates start to open.

Over the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're starting to see it finally as so many different technologies have gotten so cheap, fast, and good.

dylan604 2 hours ago [-]
So we're waiting for the Apple of the medical world to take a bunch of preexisting things to be applied together in a way that makes the whole much more valuable than the pieces. Or we need all of the individual lions to come together to make the Voltron?
ben_w 33 minutes ago [-]
Usually it takes about a decade for most medical inventions to work their way through medical bureaucracy[0], so I'd say that 10 years ago we were at the stage of watching Matthew Broderick war-dialling with an acoustic coupler and reading Usborne Books telling us that criminals of the future would work from home, and today we're in the exciting early days of dialup, AltaVista, and GeoCities[1].

[0] The covid vaccines collectively were faster only due to the fact that when money is no object you can parallelise a lot of options and can pipeline the testing stages rather than waiting for full review and another funding round before progressing to the next stage

[1] Where they-don't-tile-but-we-did-it-anyway animated gif backgrounds are the metaphor for home kits to make random things bioluminescent: https://www.the-odin.com/gfp-bacteria/

smm11 1 hours ago [-]
We already had this. It was called Theranos.
fragmede 1 hours ago [-]
I don't know if we "had" something called Theranos. In fact, I believe that was the subject of a couple of lawsuit because we didn't.
rowanG077 1 hours ago [-]
I'm not sure what this comment is trying to say. Theranos was a company build from the ground up on fraud. Apple, for all its faults, is provably at the forefront of technology used in personal computing devices.
huxley 1 hours ago [-]
I think you've captured exactly what they are trying to say
visha1v 2 hours ago [-]
the public experiences biotechnology as decades of nothing, followed by years of everything once bottlenecks align
anovikov 1 hours ago [-]
The floodgates open = the market will see that at least some of that can actually work and make money => they will pour funding => new approaches built on that funding will start working, too?
colechristensen 2 hours ago [-]
Real in vivo genetic engineering isn't going away and will indeed be a powerful tool to face cancer. Any particular effort is doubtful because this is a journey measured in decades. It is not the same story as any one particular wonder drug fizzling out to nothing, it is a class of tools that is maturing into the realm of early therapeutic deployment.
perlgeek 2 hours ago [-]
The article is pretty light on details, but

> Much like other CRISPR therapies, delivery is a critical challenge, i.e., getting the large genome-cutting enzyme to all the targeted cells efficiently.

makes me think this is in vitro so far. So, years to decades away from being available for actual treatment in humans. Still good news.

daedrdev 2 hours ago [-]
Basically the issue is often that gene therapies end up in the liver since its the livers job to detoxify, but that may cause a dangerous immune response if the immune system notices it in the liver and attacks the organ, since the person could die from the damage.
JumpCrisscross 2 hours ago [-]
I’m assuming this has been tried, but why doesn’t nano-encapsulated mRNA (that then makes the CRISPR sequences in cells) or whatever the peptide injectors do solve the problem?
amelius 2 hours ago [-]
(removed)
perlgeek 2 hours ago [-]
You can target an individual by injecting that very individual with something lethal.

If that's not what you want, you'd need something like a virus to spread it. But then you have to ask yourself: what if that virus mutates? The specialization to certain gene markers is an evolutionary disadvantage, so evolution will tend to make it lose that restriction. Ooops.

ACCount37 2 hours ago [-]
Old concern, but it really doesn't work that way. Genetics don't respect human ideas like "nationalities" or "borders" - the targeting you can get by selecting on singular DNA variants is coarse enough to make ICBMs look like precision weapons.

Like many things of this nature, people keep bringing it up because it sounds Very Scary and Very Dystopian - not because it's worth giving an actual fuck about.

ikrenji 1 hours ago [-]
I mean maybe not right now, but in 100-1000 years a complicated enough "nanobot/virus" could possibly be made to target a single person
ACCount37 58 minutes ago [-]
If it's year 2126, and you have this kind of tech floating around, and you aren't equipping the entire population with artificial immune systems capable of dealing with known and unknown biological threats? You've done something wrong.
matheusmoreira 2 hours ago [-]
I suppose it could also be used to assassinate specific persons with the precision of DNA matching. Like FOXDIE.
yieldcrv 33 minutes ago [-]
Cool. How can I help
Almondsetat 1 hours ago [-]
Can anyone point to some resources about how cancers might adapt to CRISPR treatments?
wombatpm 1 hours ago [-]
Same problem with chemo and radiation. A tumor may start off with a single cancerous mutation, but by the time it spreads there may be several. Once the cell repair machinery has been broken, the cancer cells are prone for more mutations.

Chemo, radiation, and CRISPR will kill everything it can reach that is susceptible. That leaves everything that was unreachable or resistant behind to start growing again.

Kill cancer cells is easy. Killing ONLY cancer cells is very hard.

1 hours ago [-]
zouhair 2 hours ago [-]
This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.
bonsai_spool 2 hours ago [-]
> This is why I hate patents. If CRISPR were put behind a paywall, none of this would have happened. Everything having to be about profit is getting tiring.

CRISPR was the cause of a huge patent case and likely led to a change in US patent law because of the impracticability of deciding who did something first in the laboratory.

It continues to influence research as some nations took a while to decide how they would resolve their own researchers' CRISPR claims with respect to MIT/UC Berkeley.

And yet... all the research has continued apace.

Edit: the CRISPR patent cases are continuing even today

https://news.berkeley.edu/2025/05/12/federal-appeals-court-s...

https://www.broadinstitute.org/crispr/journalists-statement-...

needSomeCoffee 1 hours ago [-]
Jennifer Doudna again. What an amazing scientist. Wow.
sssilver 2 hours ago [-]
What economic / political model would cause the society to prioritize this over adtech? It seems so unsettling that brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.
odyssey7 2 hours ago [-]
The bargaining dynamics are stacked against biology researchers at every stage of their career, from needing years and years of unrelated performance to be admitted to terribly expensive programs before they can begin to do experiments, to requiring costly equipment and resources to work, to needing to work with a small number of very powerful companies.

As a result, life science researchers are more price-taking than proce-setting when it comes to their wages / salary. If money is the motivator, then the market as-is isn’t addressing this one.

tencentshill 2 hours ago [-]
The US government funds a lot of these programs, as they are obviously in the public interest. Until one man decided to stop it.
JumpCrisscross 2 hours ago [-]
> would cause the society to prioritize this over adtech?

Private pharmaceutical R&D spending in the U.S. is around $100bn per year [1]. NIH spends another $50bn a year on biomedical research [2].

That eclipses total investments into adtech per se, which generously counted shouldn’t exceed $50 to 60bn. (And that only by counting like a third to a half of Google, Amazon, et cetera R&D and capital spending as adtech.) More precisely counted, it probably doesn’t exceed $10bn.

[1] https://phrma.org/blog/phrma-member-companies-rd-investments...

[2] https://www.science.org/content/article/final-nih-budget-202...

paytonjjones 2 hours ago [-]
When you reframe ads as "control of human attention" it suddenly makes a lot more sense why so many resources are poured into them.
abirch 2 hours ago [-]
And when you can measure how effective those ads are in changing human behavior; it's easier for businesses to spend there. As an American, I would love it if pharmaceutical companies couldn't market to consumers. It would free up money for research or lower prices.
strangattractor 2 hours ago [-]
Humans are a bunch of hairless monkeys that have evolved to scam each other rather than hunt and gather food from Nature.
ksd482 2 hours ago [-]
I don't think an economic model would work. Only a political one would work where the government would redirect a lot of funds towards this, making it a lucrative profession.

Adtech works because there is a lot of money in it. There is a lot of money in it because people seek quick entertainment, and we have a LOT of people driving the demand.

Now compare that to cancer research. There's no short term gratification about it.

9dev 2 hours ago [-]
There's a fair bit of frequency illusion involved here. A lot of brilliant human minds aren't, in fact, working on ad tech, and a lot of the people working on ad tech aren't, in fact, that brilliant (as evidenced by them working adversarially against their own fellow humans, for one).

There's a wide world outside big tech, Silicon Valley, and software in general. It only tends to be a bit less visible online.

tjpnz 27 minutes ago [-]
>brilliant human minds are trying hard, every day, to figure out how to make it impossible to bypass watching ads on YouTube, instead of helping cure cancer.

And even more brilliant minds are defeating it, every day. I have doubts about how useful they would be in a research lab.

eecc 2 hours ago [-]
I remember seeing a comic strip about this exact argument but I can’t find it any more
sourcegrift 2 hours ago [-]
Over on reddit people were debating whether cancer should be cured since it disproportionately affects rich people and it made me realise how far reddit has fallen. It's just a botnet now to manipulate elections.
projektfu 2 minutes ago [-]
The flip side is that "fuck cancer" is a shibboleth there, to the point where a headline, "[Bad person] has contracted cancer" has every comment thread starting with "First, fuck cancer."
OsrsNeedsf2P 2 hours ago [-]
After we launched our startup, we had all sorts of folks reach out to sell their GTM services. I went with one group from Vietnam that would make engagement bait Reddit questions with some accounts, and advertise our product in the comments section with others. It was expensive but it worked
yummybrainz 1 hours ago [-]
Do you think (or care) about the ethics of this sort of behavior? Do you consider it unethical and if you do, under what conditions would you decide to do it anyway?
sourcegrift 2 hours ago [-]
Reddit is a huge danger to society. There's no doubt that subs about specific non political (and non popular) topics are hugely beneficial, the overall damage the echo chambers do still outweigh these benefits.
whyenot 1 hours ago [-]
The way the voting system works at Reddit encourages group think and bubbles. All it takes is five more down votes than up votes and a comment or post essentially disappears from view. It's a design that actively avoids debate.
polshaw 10 minutes ago [-]
That's a huge misreading. Hiding comments in the UI empirically does not suppress discussion, if anything it actually attracts engagement. Lots of people are seeking the "wrong" to "correct" it.

Suppressed debate is almost universally due to biased/captured moderation teams aggressively using bans.

mannyv 54 minutes ago [-]
Well, now that it's becoming "the community source" for LLMs it's becoming even more of a target for large-scale manipulation.
egeozcan 1 hours ago [-]
Just spend 15 minutes in /b/ and everything else will feel better.
sebzim4500 2 hours ago [-]
I'm certain that is not a mainsteam opinion on reddit, but by its nature you will be able to find arbitrarily stupid opinions in individual echo chambers
airstrike 1 hours ago [-]
I am not so certain
toraway 1 hours ago [-]
I would imagine the charitable characterization of that discussion is much closer to “awesome, this will mean the Peter Thiels and Elon Musks of the world will live to 150 while both me and my children will be dead long before this trickles down to regular people” vs. “we shouldn’t cure cancer”.
vitalyan1234 1 hours ago [-]
>reddit

>children

stepchildren, perhaps.

Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact
Rendered at 18:38:08 GMT+0000 (Coordinated Universal Time) with Vercel.