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

innovativegenomics.org

171–180 of 239 posts

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

#171
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.

Have you tried just mashing on the keyboard and seeing if a great comment comes out?

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

#172
post #164

Earlier quoted context omitted.

I haven't written about it publicly, but I can elaborate here. I don't mind answering further questions about it even if you believe they'd make me uncomfortable - they won't. I've come to terms with what's happening to my body and that I may not benefit from my efforts. Background: ~3 years ago I was diagnosed with a very rare MPLW515L-driven blood cancer known as a myeloproliferative neoplasm. My hematopoietic stem…

This is so impressive - kudos to you. Thanks for sharing and being open to questions. How much overall has this costed you? Do you think that a middle-class person could afford to do what you did? > So, I laddered up the academic food chain using a little cash (donations), emails, airline tickets, and conference admission. ~2 years after my diagnosis I found myself in a closed-door session called the MPN Roundtable i…

> How much overall has this costed you?

For this project, seed capital low six figures. I am collaborating with family and friends, non-profits, and using doubling mechanisms available to me to at work to fund the very early speculative bench research. This is where we are and its sustainable today.

Once we have the basic tech worth scaling up - to raise the first round of capital, I estimate $1-2m with a wider friends & family and angel investor round. This will be early de-risking research and delivery mechanism testing.

Beyond that I can see a path to a ~$20m round to further de-risk any assets that come out of these speculative efforts, but I haven't gotten this far.

In rare disease therapeutics the challenge isn't raw capital, it's finding the _right_ capital that understands how assets like these get de-risked and can tolerate the shape of the upside. Anything CRISPR-based is usually not a chronic therapeutic, so that disqualifies most of big pharma. Acute, curative technology like this requires informed capital.

> Do you think that a middle-class person could afford to do what you did?

Yes.

In the rare disease field even a small amount of capital attracts enough attention to have meaningful conversation with bench researchers. If you're willing to travel to the niche conferences, ask dumb questions, grind out the studying, and approach the speakers after their sessions.

Researchers respect people who do their homework and mobilize to meet them. They want (need) to hear from patients and caregivers - so they tend to listen very carefully.

Fun fact: I've had multiple researchers ask me for samples of my bone marrow. Has only happened in-person :)

> Why don't they allow recordings at the MPN Roundtable? It could be useful for others to learn from.

I don't know, it's been going on for a while. I can speculate: they're discussing pre-publication data, some of which had come out of their labs only hours prior to their presentation. It's completely unfiltered. I think there's real risk of some of the things that are shown being sensationalized or taken out of context.

The audience is trained and practiced in keeping a sober, skeptical lens on everything they see - so it's more about the debate and tear-down of the early data for the betterment of the niche.

There's zero attempt to hide anything, it's just a forum for collegial debate.

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

#173
post #67
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…

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.

> I would deal with this by deciding how many cells I want to kill each day

Yes, this is an approach. This starts to exceed my understanding of the problems the teams are facing - but there are concerns about the efficacy of Cas12a2-based approaches fading. Not because the cells adapt, but because your immune system starts acting funny in the presence of the payload.

I don't recall the specifics but there seems to be a window of opportunity for these things.

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

#174

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…

Do mammals have a CRISPR analog?

Background on this question: CRISPR-Cas is a naturally occurring process in bacteria that is used to adapt to viral attacks. We've coopted the system for use in mammals.

As far as I know a few labs in this space are operating under the basic question, "why haven't viruses killed everything by now?"

So this category of research is more or less the answer.

> Do mammals have a CRISPR analog?

Not exactly. There are things like https://en.wikipedia.org/wiki/Ribonuclease_L that nuke cells and are stimulated by interferons. This might be why interferon injections are common chronic therapeutics for diseases in this space.

The closest thing we have is probably whatever adaptability B or T cells can muster on their own? I'm sure someone lurking in the comments has a better answer.

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

#175
post #110

Earlier quoted context omitted.

The point of going slowly is that we make sure something works, even if it has these bad side affects. Do we try experimental drugs with worse effects so that we can find effective ones faster? There are brave souls out there who will participate in clinical trials or experimental exceptions

Typically what happens is that the new treatments with bad side effects are given to the sickest patients (who have exhausted all other mechanisms), rather than to the bravest souls with less dire current circumstances. This makes some sense in terms of compassion and matching new experimental techniques with patients with no hope, but it skews the results highly negative because the patients are already very close t…

> It does not provide an accurate signal for what the results would be if we gave them to less sick people.

It provides an excellent signal because we want to prove that these drugs are doing something that the standard of care is unable to.

There's this sense that medicine is easy and some evil cabal are limiting health to their cronies. Most medications never get to trial for their intended indications, and most fail trials. There's no reason to believe oncology medications are somehow uniquely unlikely to go through this well-described process of failure.

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

#176
post #161

Yes! I have a genetic disease that will take me out in my 70s and I’m really hoping CRISPR gets to it before I do!

A lot of people's genes will take them out in their 70s but cheers to crispy

Very true!

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

#177

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.

Yeah. With cancer, delivering to 99% of the cells won't cut it, the surviving 1% will quickly grow back.

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

#178

Earlier quoted context omitted.

Indeed, there's no "be a better/stronger cancer and spread more effectively to more hosts" the way there is with bacteria or a virus. It's not like the flu where we need a new shot every winter because every winter is a new flu. 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 t…

>there's no "be a better/stronger cancer and spread more effectively to more hosts" 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.…

Right, but that's within a single host isn't it? Like patient A gets that mutation and succumbs, that sucks, but the stronger cancer cells don't them jump to patient B the way antibiotic-resistant bacteria do.

(barring the transmissible cancers article that your sibling comment linked to, but that's not the common case)

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

#179
post #87

Earlier quoted context omitted.

Indeed, there's no "be a better/stronger cancer and spread more effectively to more hosts" the way there is with bacteria or a virus. It's not like the flu where we need a new shot every winter because every winter is a new flu. 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 t…

> Indeed, there's no "be a better/stronger cancer and spread more effectively to more hosts" the way there is with bacteria or a virus. The rare exception: https://en.wikipedia.org/wiki/Clonally_transmissible_cancer

Well that's terrifying, TIL.

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

#180

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…

> We might have "AI" ...

Basically everything that was invented up to 3 years ago was invented without the help of "AI". And that includes "AI" itself, for we, humans, invented that too.

So yup, humans can be quite resourceful.

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