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CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

innovativegenomics.org

131–140 of 239 posts

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#131
post #5

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.

> 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.)…

One of the primary challenges of drug and device economics is the long lead time between capital deployment and returns. One of the selling points of tech is speed to Market.

Factors that would make it more attractive our lower interest rates, higher returns, or faster development.

All of these are theoretically possible to adjust, but the last is most feasible to do in a tailor-made way through FDA review and approval reform. An ambitious example would be allowing conditional Market approval after Phase 2 and treating phase 3 deliverables as post-market commitments.

Advancing the revenue curve two to three years while maintaining the same patent expiration dates can dramatically change the ROI of a pharmaceutical development program.

Beyond this, even conditional Market allowance allows firms to better gauge Market interest and validate Financial investment models sooner.

Similarly, there's also some really low hanging fruit in this area to help manufacturers get to Market faster. For example, the FDA approval of trade names and label content is one of the last steps in Market authorization. Moving this earlier in the process would help products itself sooner and start producing Revenue sooner. Imagine having your billion dollar annual revenue shift out a quarter because the FDA wanted some last minute change to how a cartoon belly button looks in the instructions for use.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#132

Earlier quoted context omitted.

"When have you most successfully hacked a non-computer system to your advantage?" Amazing resourcefulness, you should consider applying to YC if you haven't! And I hope you manage to find a solution to your problem it sounds very promising.

And by the way, when Anthropic (sic) tells you that it's too dangerous to allow GPT-2/GPT-3/GPT-4/GPT-5/Sonnet/Opus/Mythos/Fable to discuss human biology, and some of us object vociferously to their premise, this is what we're talking about.

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Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#133

Does anyone know a website where I can see/read of how many cancers (and their variants) we've effectively solved, have drugs to negate their effects, have experimental drugs for and uncurable cancers? I think that graph would be awe inspiring looking at the past decade of advancements. What's more crazy is that we're slowly going from millenia, to decades, to likely years in the near future from being presented a bi…

Have you asked Claude to pull this and graph it over time? It could build a static site as well.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#134
post #50

Earlier quoted context omitted.

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…

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!

> Are there any plans to move to in vivo?

Yes! That's the next step. There wasn't a mouse model for my variant so they're building that, too. But in vivo testing should be underway this calendar year.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#135
post #133

Does anyone know a website where I can see/read of how many cancers (and their variants) we've effectively solved, have drugs to negate their effects, have experimental drugs for and uncurable cancers? I think that graph would be awe inspiring looking at the past decade of advancements. What's more crazy is that we're slowly going from millenia, to decades, to likely years in the near future from being presented a bi…

Have you asked Claude to pull this and graph it over time? It could build a static site as well.

Isn’t this likely to lead to inaccurate data? I wouldn’t know enough about the domain to fact-check Claude.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#136
post #62

Earlier quoted context omitted.

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 collater…

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 cert…

> I don't think that more than sloppy accuracy is acceptable for any gene therapy

Valid critiques of Cas12a2 must acknowledge the mechanistic differences between Cas9 and Cas12a2. There is no research to suggest Cas12a2 is "sloppy" and significant research that demonstrates it is not "sloppy."

I appreciate the skepticism but I would encourage you to study the actual mechanism discussed in the paper.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#137
post #84

Earlier quoted context omitted.

Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells? Like, it stops surfacing some cholesterol receptor because the drug is being delivered by LNPs that target that receptor, and now the cell is starved for cholesterol? 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 eff…

>Depending on how the LNPs are designed, would resistance also potentially cripple the cancer cells? 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.…

Interesting, thanks for the info!

Another question: how does this approach compare to trying to repair the pathogenic variants in the cancer? I asked here about that approach recently and the response was mainly about delivery difficulties: https://news.ycombinator.com/item?id=48285386

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#138

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 fut…

You're confusing the beurocratic FDA stamp of approval with safety and effectiveness. Those are not the same thing.

Re: CRISPR tech selectively shreds cancer cells, including "undruggable" cancers

#140
What stands out to me is how cancer therapy keeps moving from broad destruction (chemo/radiation) toward increasingly precise identification of malignant cells. The challenge no longer seems to be "can we kill cancer cells?" but "can we reliably identify only cancer cells and reach all of them?" This paper looks like another step in that direction.
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