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The post on AI and and cures for cancer is https://www.writingruxandrabio.com/p/a-response-to-dario-amo... .
Nature - https://www.nature.com/articles/s41586-026-10738-7
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.
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.
It’s only a matter of time before the next better thing shows up.
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?
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.
I usually end Legend after the mannequin trap, and end Sunshine after the transit of mercury.
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).
Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.
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.
mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
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.
[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/
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
I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
Yes, if the LNP could be engineered to target an essential surface receptor, which is still a very tough problem. It would also not solve the issue of the payload successfully entering the cell but being subsequently degraded.
>I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.
Once we solve the cancers we know about, they're solved forever, with the one caveat that more people will live longer, so that will increase the window for eventually still ending up dying to one of the cancers that happens to have a non-evolved built in resistance to this or that treatment. Which is a great deal of course, especially if it's a treatment that sounds way less destructive of QoL than chemo, radiation, etc.
No, but there is "be a better/stronger cancer cell and don't succumb to whatever therapy is killing its neighboring cells." It's exactly akin to how dosing isolated populations of bacteria with antibiotics selects for individual cells that are resistant, which then multiply and dominate [0], just like a tumor.
[0] https://www.youtube.com/watch?v=plVk4NVIUh8
The rare exception: https://en.wikipedia.org/wiki/Clonally_transmissible_cancer
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/
> 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.
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.
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.
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.
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.
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...
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.
There's a wide world outside big tech, Silicon Valley, and software in general. It only tends to be a bit less visible online.
And even more brilliant minds are defeating it, every day. I have doubts about how useful they would be in a research lab.
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-...
>children
stepchildren, perhaps.