Is CRISPR the cure to cancer and ageing?

Is CRISPR the cure to cancer and ageing?

It's just for produce man

no

Love

Cancer, sure. IT's only a matter of time before we edit our own body cells to destroy cancer cells. Should be done within 5-10 years at least. Ageing is a whole other beast though and I doubt that will be solved within our lifetime desu

It's not that simple.
CRISPR is a tool while lets you make precise changes in DNA. Doesn't help unless you know what change to make. If you know that a flaw in gene X causes disease Y, that's fine. You can do something about X. But we don't understand aging.

There's also the fact that biochemistry is complicated and it's harder to do just one thing to a genome than it is to change one thing in a complex computer program without causing 'side effects'. A change HERE may have unforeseen consequences THERE.

inb4 CRISPR is used to make human telomerase and we all become lobster/human hybrids

it's already been done with specific cancer in experimental treatments. 5-10 years for FDA approval tho

>DUDE CRISPR

I hate how popsci has taken Crispr stuff. Cas9 is literally a molecular pair of scissors. It cuts. That's it.

Any sort of edit you want to accomplish relies on repairing that cut in a certain way. People need to stop acting like Crispr is this black box that does everything under the sun as far as genetic engineering. It cuts. That's it.

So, when will I be able to glow in the dark?

how long till hobby bio-technicians are pirating top shelf pharmaceuticals in their garage and basically put every large drug company out of business?

(realistically tho, they'll outlaw it in America, jack up the prices of drugs and blame pirates for it, and 3rd world shithole countries where the laws don't apply which could never get these drugs before will have better drug availability than any 1st world country)

Bruh shitty countries already have unregulated pharma products and the result is a market flooded with knockoffs that don't do anything, irregular dosages, or incorrect syntheses. If you like the idea so much, start taking the same meds but produced in India.

>Any sort of edit you want to accomplish relies on repairing that cut in a certain way.
This can be done quite simply by reinserting the "normal" form of the gene via Homology directed repair.
>It cuts. That's it.
Wrong. New technologies using CRISPR have been able to physically change base pairs and upregulate certain genes

>CRISPR as a tool for synthesizing APIs

The cure for cancer was found ages ago actually. The jews have been suppressing it because of muh shekels.

>This can be done quite simply by reinserting the "normal" form of the gene via Homology directed repair.
As someone who does HDR/NHEJ on the daily, I can tell you "simple" is a terrible word for it. Maybe the design is simple (generating homologous oligos and ordering them from IDT takes about 5 minutes), but certainly not the execution.
>Wrong. New technologies using CRISPR have been able to physically change base pairs and upregulate certain genes
The first thing you allude to is an evolved protein that works in conjunction with dCas13 or dCas9. The cas system protein just functions as a mechanism to target a region. The actual edit is accomplished by a novel protein. This is a great example of how new biotech news is filtered down to "DUDE CRISPR". The actual, important information was that the researchers developed a novel protein that converts adenine to inosine. But because they used Cas proteins to target the action of the novel protein, the news devolved into DUDE CRISPR.

As for up regulating certain genes, that's accomplished through swapping out native promoters for other promoters of differing strengths. Here you can use Cas9 to target your gene of interest, but again you need another mechanism to actually accomplish the edit.

Yeah so as we get better with this technology there are endless possibilities. Pretty much all monogenic diseases will be eliminated i.e. CF and Huntingtons. That's not even a "DUDE CRISPR" exaggeration, it's just a fact, then we can use it to tackle more complex things such as cancer which it will no doubt have an essential role in playing

You seem like an expert in this topic. What are the realistic therapeutic applications of this technology in your opinion in the next 10 years

Oh yeah don't get me wrong, the potential for the technology is insane, but we're not there yet and the tendency to use "Crispr" as a catchall for anything remotely related to Cas systems has created a lot of problems in understanding. It's like how people call everything software related an "app".

From my own experience, Cas systems are phenomenal at cutting. I regularly see 95+% cutting efficiency. 80% would be a bad day, which is still way beyond other methods. Compare to traditional HDR through loop in/loop out, where your maximum theoretical efficiency is 50%.

But the problem is all the cool shit people talk about in terms of the potential for Crispr/Cas technology relies on what happens after the cut, which we're still really crappy at doing. That's basically where I see the technology/industry right now. We've gotten really really good at targeted cutting of DNA, but we need to make significant improvements in the technology for what comes next.

There's a shitload of genetic diseases that have the potential to be cured. How that actually occurs will depend on the specific case. There's a gene therapy trial underway right now trying to use zinc fingers to treat Hunter syndrome. It's a great disease to target for an early attempt at gene therapy because they only need an editing efficiency of 1% of the patient's liver cells (to get them to produce an enzyme the patient lacks) to be successful. Other genetic diseases that would require higher editing efficiencies would of course be trickier.

I think it's highly likely that we will see gene therapies using Cas proteins in some way (usually for targeting the right locus) cropping up. Per your timeline though, 10 years is a bit short to see this technology go from the lab to people. Right now it takes about 10 years for a conventional drug to go from a lab concept, development, human trials, and FDA approval before finally reaching the market. Gene therapies are a totally new world, so I would expect a longer and more rigorous approval time.

this

>There's a gene therapy trial underway right now trying to use zinc fingers to treat Hunter syndrome.
Does CRISPR's potential outweigh ZFN or are they basically the same thing?

Cas proteins and ZFNs are both ways of creating a double stranded break at a targeted location. ZFNs have been around longer and have more history, which is why the current trial is using them.

Looking forward, ZFNs are really difficult and expensive to create, while Cas systems are comparatively cheaper and significantly easier. Cas proteins are definitely the future.

Would you say the main barrier for treatment now is delivery at a target site?

The way I'd put it is that there are challenges entering the cell and challenges once you're within the cell.

Within a single cell, you need to deliver everything you need to accomplish the edit you want. At the very least this is a Cas protein and your guide RNA. It could also include repair fragments and/or associated proteins (ie using dCas9 to target a gene, while you use another protein to edit it).

Once everything is in there, Cas9 is great at targeting the gene and cutting it, but that's not enough, you need repair to happen. If you're relying on a knockout by NHEJ, you just have to hope the gene doesn't happen to repair in a way that removes the PAM while also keeping the gene of interest functional. If you're relying on HDR, you need your repair fragment and the necessary proteins to diffuse to the right spot and work their magic. Anything short of that, and you fail editing or the cell just dies.

Then in multicellular systems, you need to target enough cells simultaneously to achieve your desired effect.

Right now a lot of people are working on ways to improve these issues. Novel delivery systems for Cas and other shit, recombinases to make HDR happen more readily, etc.

>just have to hope the gene doesn't happen to repair in a way that removes the PAM
Forgive me for the brainlet question, but aren't PAM sequences only found in viruses or are they in all cells?

So the guide RNA you use to have Cas9 target the genome is called the protospacer. PAM stands for protospacer adjacent motif, it's the sequence after the protospacer that the nuclease actually recognizes to cut. When Cas9 is used in bacterial cells to defend against viral DNA, it cuts the viral DNA at the PAM region.

For Cas9, the PAM is any NGG region in the genome. So for your Cas9-guide RNA system to work, there has to be a NGG region right after your protospacer. Different Cas type proteins have different PAMs.

>Is CRISPR the cure to cancer and ageing?

No. I haven't personally worked with CRISPR/Cas9, but I've read many papers where it's been used. It is tricky to deliver plasmids in such a way that they're actually used when Cas9 cuts the DNA. Cells engineered with CRISPR have to be selected out of an overwhelming population of cells that failed to actually uptake the DNA.

What this means in a clinical context is that if you tried to use CRISPR on patients, you would find that it wouldn't actually work on most of the cells, and the genetic changes you've imparted would quickly be lost via genetic drift.

It's not a meme technology though - it's excellent for studying the genetics of disease by making knockout models and such. But it's not like some magic marker that you can inject into patients and edit their DNA like a text file on a computer. Lots of unfortunate technical limitations prevent that.

It's more about what genes are being edited on top of a (presumed) human-safe technique. If you have a fast car but nowhere to go, you're still going nowhere.

For cancer? It's probably going to be -part- of a cure for -some-, hopefully many, types of it. Aging? Nah. It'll help therapies but to "cure" aging implies immortality and you really, really would not want me to get started on how dangerous/jumping the gun it is to imply that understanding some parts of aging and being able to modify lifespan in model organisms = immortality's on the horizon. It's not. That's slightly like saying that when humans started poking each other with sharp sticks that nukes were just around the corner, because they're both weapons and weapons research had begun at that point. Aging research has only really been going in earnest for about 20-30 years and only really blossoming the past 5-10ish.

As for the technique itself, sure it's incredibly useful but it doesn't actually change what was possible before, just makes it much faster and easier.

It's like this: Say, in the 90s most people had dial-up. This worked for internet access, but if you wanted a specific use of the web then you'd possibly have to devote your connection all night to downloading a movie or program or whatever. Your connection is also much more unstable and your download could be wrecked if someone picked up the phone. Today, you have whatever broadband and can get the same movie much faster and more conveniently, to boot with one of the old risk factors now irrelevant.

Similarly, gene editing tech has been commonly used since the 90s. There are lots of tedious methods but, they (hopefully) work. Crispr allows much faster and simpler editing with higher success rate and with the bonus of being able to attempt to target where your edit goes into a genome, partially negating an old risk factor of being unable to control where it went (and hence greatly increasing the risk of causing cancer etc).