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

innovativegenomics.org

221–230 of 239 posts

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

#221

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…

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

#222
post #164

Earlier quoted context omitted.

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 frien…

Do you feel that recent advances in AI can speed up such rare disease research?

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

#223

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…

#TIL multiple myeloma went from being a death sentence in the 90's to quite manageable using a really old compound called thalidomide[1]. Though it sad that it was exploited for almost two decades to line the pockets of a dozen rich a*holes.

[1](https://www.propublica.org/podcast/revlimid-cancer-drugs-fda...)

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

#224
post #190

Earlier quoted context omitted.

Well, depending on how cynical you are. I'm sure there are those that are happy to let the 'senecent' people die of cancer and have a younger population and healthier population pyramid. Getting older, I'm not subscribing to that, but it sometimes feels like the RFKjr -style interventions are calculated. Then again, this theory makes zero sense when dismantling herd status for measles (I don't think 'natural measles…

Wow, I’ve joked about the prospect so frequently that realizing it has a real Twitter subculture hit me hard. Describing people like that… it’s akin to derisively referring to “the dysfunctional” part of society, to pick on my own disability. The parallels to the Nazi’s ableism are pretty hard to ignore :( But on a lighter note: is there any belief more certain to spoil?? My god. Don’t underestimate the moral worth o…

I think humour is the best medicine. EG, why not kill all the poor: https://youtu.be/s_4J4uor3JE

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

#225

Earlier quoted context omitted.

>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)

Sure, but my point is that convergent selective pressure across different individuals' tumors is strong enough that they independently arrive on the same resistance mechanisms to a given therapy, e.g. [0]. Just like if you performed the same bacterial antibiotic resistance experiment [1] across multiple independent trials, you'd repeatedly get the same result.

[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/

[1] https://news.ycombinator.com/item?id=48505231#48507925

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

#226

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…

I would guess you did not first write “CRISPR is an overhyped approach”, then after careful reflection decide, I don’t think that quite captures the intensity, better go with “extremely overhyped”. The comparison is kind of a category error. One is a DNA editing technique and the others are deliver platforms. I recall the hype mostly being how revolutionary it could be, not comparing it on a timeline to specific tech…

it's revolutionary in genetic research, allows us to observe cells with specific gene knockouts, over activations, etc. it's just very hard to deliver to a whole system

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

#227
post #191

Earlier quoted context omitted.

That doesn't seem to be true, the global expectancy is 73 and only a dozen of the wealthiest countries are mid 80s. I wouldn't be worried about dying at 70, but maybe I'm built of tougher stuff.

You say my claim is not true then proceed to acknowledge it is true. To be clear about the fact: about 1/4 of all countries have a life expectancy >80, and as you said, more than a dozen in mid-80s.

Well, no, no country on earth has an expectancy in the mid 80s, I was being generous with your wording. 40-50 countries have expectancy between 80-84, which is early 80s. Most countries are sub-80.

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

#228

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…

Exactly.Now these are the kind of matters the world should be more inclined to invest in.

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

#229
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…

> I don't think any of this can be changed without large-scale social acceptance of greater risk in clinical trials and significant support from the government.

I agree with you about significant financial support from the government if that support is financial and given to smaller groups.

I disagree about societal acceptance though. I feel like your point of view may be missing clinical trials and treatments in the USA. The laws we have are written in blood, and the laws more sophisticated than I think you appreciate.

There are various options for fast-tracking drug development if the conditions are serious enough or the drugs promising enough. I suggest actually reading about how these processes work, and the history of what happens when we don't have these protections, before deciding that approvals are overly cautious.

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

#230
post #194

Earlier quoted context omitted.

Surely a far simpler way to evolve resistance would be a trivial mutation in the p53 transcript that the guide RNA is looking for.

In practice, you’d use multiple guides targeting multiple mutations, so that the probability of having/acquiring multiple resistance mutations abrogating every guide from binding would be infinitesimal.

LNPs have limited capacity, and if the CRISPR/Cas system they’re using requires an exact match, then any additional point mutation or insertion or deletion in the segment being matched would allow the cell to survive. I suppose that approximately 3n extra guide RNAs (where n is the length of the matched sequence) could be added, but that seems a bit messy.
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