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

innovativegenomics.org

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

#71

Post by polshaw »

whyenot wrote: post #41
sourcegrift wrote: post #24

Earlier quoted context omitted.

Reddit is a huge danger to society. There's no doubt that subs about specific non political (and non popular) topics are hugely beneficial, the overall damage the echo chambers do still outweigh these benefits.

The way the voting system works at Reddit encourages group think and bubbles. All it takes is five more down votes than up votes and a comment or post essentially disappears from view. It's a design that actively avoids debate.

That's a huge misreading. Hiding comments in the UI empirically does not suppress discussion, if anything it actually attracts engagement. Lots of people are seeking the "wrong" to "correct" it.

Suppressed debate is almost universally due to biased/captured moderation teams aggressively using bans.

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

#72

Post by shevy-java »

Bjartr wrote: post #60
roncesvalles wrote: post #55

Earlier quoted context omitted.

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 gene…

Edit every cell? No. Edit enough cells to impact health outcomes for a meaningful period of time? [Yes]( https://www.youtube.com/watch?v=J3FcbFqSoQY )

This approach can work for some genetic diseases such as blindness based on some cells in the retina or partial blindness. For others this is not really a cure. If you want to cure people with progeria, does curing 20% of the cells really help? Perhaps 100% is not necessary, but it would seem strange to cure only some cells but not others. You'd have a mosaic of cells where some would work and others don't. Cells interact; timing also plays a role in development. I don't really see that aiming for anything but a very high number of cells cured, can work.

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

#73

Post by shevy-java »

perlgeek wrote: post #61
ordinaryradical wrote: post #32

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…

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…

Why does it take 20 years? Except, of course, that it does not work nowhere near as well as it is being promoted - aka hyped.

mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.

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

#74

Post by projektfu »

roncesvalles wrote: post #55
ordinaryradical wrote: post #32

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…

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 gene…

I disagree that it's "gene therapy" to affect the natural regulation of mRNA production. If that were true then the term "gene therapy" loses its meaning, as just about everything changes the expression of mRNA. You can probably do so somewhere just by thinking really hard about it.

Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.

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

#75

Post by cyberax »

MontyCarloHall wrote: post #70

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…

There are some ideas about making it triggerable. So first you load the cells with a protein that is ready to start shredding but is inactive. Then you trigger it with a second compound.

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

#76

Post by AnimalMuppet »

MontyCarloHall wrote: post #70

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…

But cancer isn't an organism. Cancer cells in any specific individual may evolve that way, but "human cancers" as a group will not. (The only way they could is by evolving human DNA, but "survival of the fittest" pushes the opposite direction for that.)

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

#77

Post by projektfu »

sourcegrift wrote: post #16

Over on reddit people were debating whether cancer should be cured since it disproportionately affects rich people and it made me realise how far reddit has fallen. It's just a botnet now to manipulate elections.

The flip side is that "fuck cancer" is a shibboleth there, to the point where a headline, "[Bad person] has contracted cancer" has every comment thread starting with "First, fuck cancer."

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

#78

Post by cyberax »

shevy-java wrote: post #69
spligak wrote: 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…

> So the question is: how do you detect specifically only cancer cells via lipid nanoparticles?

You don't. Healthy cells will also get these nanoparticles, but without the triggering DNA sequence, the mRNA payload will remain inert and eventually will be degraded.

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

#79

Post by MontyCarloHall »

AnimalMuppet wrote: post #76
MontyCarloHall wrote: post #70

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…

But cancer isn't an organism. Cancer cells in any specific individual may evolve that way, but "human cancers" as a group will not. (The only way they could is by evolving human DNA, but "survival of the fittest" pushes the opposite direction for that.)

Nonetheless, we see the exact same resistance mechanisms to the same therapies recur across individuals, e.g. [0]. Convergent evolution is a harsh mistress.

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

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

#80

Post by ordinaryradical »

Gethsemane wrote: post #63
spligak wrote: 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!

Seconding this comment. I would love to read a write-up about your experience and how you’ve been trying to work on solutions for yourself. Stories like these are valuable to the field and inspiring to other folks dealing with a tough diagnosis.
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