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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.

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.

Viral vector delivery is indeed harder to sell with PopSci, what with movies like "I am Legend".

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).

“Virus” - that’s why.

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.

Bingo! CRISPR has an advantage of being relatively easy to describe to a layman, giving it a PR advantage.

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.

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.

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.

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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.

> 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-...

Just spend 15 minutes in /b/ and everything else will feel better.

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

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

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”.

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.

> 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...

When you reframe ads as "control of human attention" it suddenly makes a lot more sense why so many resources are poured into them.

Humans are a bunch of hairless monkeys that have evolved to scam each other rather than hunt and gather food from Nature.

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.

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.

I remember seeing a comic strip about this exact argument but I can’t find it any more