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18 hours ago by keven

For people interested in Crispr, Rich Horgan started a non-profit called Cure Rare Disease working to fast-track customized therapeutics for his brother and other families with Duchenne Muscular Dystrophy using in-vivo gene editing.


6 hours ago by nerdkid93

I was super pumped for this tech to start being used in human clinical trials, but a couple of years ago, there was a study[0] that raised some key concerns about CRISPR therapeutics increasing the risk of cancer due to some edited cells self-destructing once their genomes have been modified, leaving behind cells with a higher risk of cancer due to not being as sensitive to genomic edits. Have these challenges been overcome yet?

[0]: https://www.scientificamerican.com/article/crispr-edited-cel...

4 hours ago by suifbwish

Woah! So the cells that accept the CRISPR modifications do so because they have dysfunctional p53 gene activation. This most likely means they are specifically the cells most likely to become tumors if they undergo any mutations triggering carcinogenesis as p53 and its helper genes are mainly responsible for killing off cells that become cancerous among other things.

This means that you can use CRISPR to selectively kill these cells only since they would be the only ones that easily accept and express the CRISPR modifications. This could be ground breaking if it is not already tried.

19 hours ago by godmode2019

Can someone answer, what is the entry method of CRISPR in adults, don't it need to change all instances of a cell to be effective?

I don't really understand the delivery method.

19 hours ago by azernik

Brute force:

"...some of the patient’s hematopoietic stem cells... [are] harvested for gene editing outside the body. After these cells are removed, the remaining bone marrow is destroyed with chemotherapy to allow space for the repaired and reinfused stem cells to grow."

EDIT: This is apparently the same procedure as conventional bone marrow transplants in SCA patients. CRISPR is just slotted into that workflow to synthesize a transplant, without needing to find a donor.

19 hours ago by liamwire

Even with the amount of hype around CRISPR, that is... incredible. Turning patients into their own donors feels magical.

I suppose in this instance, the patients wouldn’t need immunosuppressants after their treatment, as I’d expect standard care patients currently need for life?

18 hours ago by rcthompson

I think it's an open question. After this treatment, the patient's red blood cells will be producing a new protein that they have never produced before. This protein only differs from the previous one by one amino acid, so the question becomes how sensitive the immune system is to such a change. Given that the immune system has some difficulty recognizing cancer cells with multiple protein-coding mutations in them, I think it's likely that a single amino acid change will fly under the radar and not require any immune suppression, at least for the vast majority of recipients of this treatment.

17 hours ago by quiescant_dodo

The fundamental idea of using the donor's own stem cells is known as an Autologous Stem Cell Transplant and has existed for a while. It is used as therapy for a fair number of blood cancers (e.g. multiple myeloma or a few leukemias).

Using "something" to manipulate the donor cells has also been done for these autologous HSCTs. I know of "CAR T cell therapy", but there are likely others. ( https://www.cancer.gov/about-cancer/treatment/research/car-t... )

I think some small number of autologous HSCT recipients require immunosuppressants, but from what I remember the number is very very small. (Allogenic HSCT recipients, who receive cells from a different person, are _much_ more likely to require lifetime immunosuppressants.)

It's super cool that they're able to treat genetic diseases this way!

19 hours ago by causality0

But does the CRISPR method require the patient to remain on anti-rejection drugs the rest of their life?

18 hours ago by Gibbon1

I would assume more likely not since they are the patients own cells.

18 hours ago by undefined


19 hours ago by undefined


19 hours ago by mbreese

Because this is a blood based disease, I’m guessing they would extract blood from the patient or extract them from bone marrow (more likely), treat the cells outside the body, and then transfuse the modified blood cells back onto the patient to try and engraftment them in the bone marrow.

All of the hard CRISPR stuff is likely in vitro.

However, I don’t know anything about what the specific plans are though, this is just speculation.

12 hours ago by konschubert

For blood diseases it’s enough to replace all blood-producing cells and their producers, I guess?

18 hours ago by refurb

Sickle cell anemia can be "cured" by inducing expression of fetal hemoglobin (fHb). You don't need to shut off the defective gene and the disease is effectively "cured" if you replace enough scHb with fHb.

So you remove bone marrow from the patient, modify the cells, put them back in. The modified cells produce fHb at a high enough level that symptoms of Sickle Cell go away.

Not that different than the already approved CAR-T therapies (with the exception they don't use CRISPR for the genetic modification).

18 hours ago by maxerickson

This treatment modifies the adult hemoglobin gene.

20 hours ago by xiphias2

Hasn't Vertex already run an experiment on people and cured sickle cell disease using CRISPR last year? What's new here (except that the organizations are different)?


20 hours ago by maxerickson

That trial deactivated a gene (causing a different one to be more active).

This trial is inserting/editing a gene.

20 hours ago by xiphias2


9 hours ago by codeproject

Two years ago, Chinese Scientist Dr.He JianKui did a very similar thing. He edited the genome of twin girls so that they will be immune to the HIV-virus. By all account the project is successful. The announcement of this breakthrough causes a lot controversies. People are shocked and dismayed. Here is the link: https://www.nature.com/articles/d41586-018-07545-0

8 hours ago by meepmorp

Using CRISPR to edit the genomes of human embryos because YOLO, is very different to using it in a modified version of an existing treatment for sickle cell anemia. Do you not see the difference in ethical scale and scope?

8 hours ago by WaitWaitWha

>Do you not see the difference in ethical scale and scope?

I agree with you that to you (and me) in this case there is a difference.

But, who sets the scale & scope?

(I am aware that the box has been opened, it will never be closed.)

6 hours ago by downrightmike

HIV is a very capable mutator, all he did was give it a chance in two hosts to mutate against. and then who knows the future danger of the kid's health. Dolly the sheep was cloned, but had enlarged organs. So not perfect. And what changes in these kids is a huge unknown and there was no way to predict it, because the doc just did because he could. Plus a whole eugenics program has a huge historical negative example in the last century because it lead to death camps.

8 hours ago by codeproject

Totally Agree!!! it is the initial stage.

8 hours ago by codeproject

if you read the Original Article close enough, You will see the subtle point here:

>If this is successfully applied in young patients, it has the potential to prevent irreversible complications of the disease

How young is this going to be, One years old, 1 month old...

7 hours ago by meepmorp

Bone marrow transplants as a treatment for SA are already a thing. All this does is make it so you can use the patient's own bone marrow instead of a donor, hopefully reducing rejection. There's no subtle point to be made, the question you're asking is a solved one, because it's just a modification of an existing therapy.

Now, compare that to editing human embryos in vitro then implanting them, just because you want to prove it's possible to use a gene editing technique to alter the genome of a person.

8 hours ago by pitspotter

Trying to enhance or disable healthy genes isn't the same as fixing known disease-causing mutations.

Moreover, identifying harmful mutations can't tell you how to build superhumans. So I think the similarity is only superficial.

8 hours ago by codeproject

He JianKui's Project is not to build the superman. the parent of the baby girls is HIV positive. He did that so that Parent is not going to worry about their babies is going to get the disease.

7 hours ago by ngcc_hk

For now.

Helping China to trade is not to build a totalitarian country as well. Just trade.

14 hours ago by pmlnr

I honestly thought my generation will not yet live through Gattaca; seems like I was wrong.

9 hours ago by pitspotter

Curing genetic diseases is going to turn unlucky people into more normal people, not privileged people into superhumans.

8 hours ago by gomox

Given the history of humanity, I find this take to be anywhere between optimistic and naive.

8 hours ago by meowface

The parent said "curing genetic diseases", not "CRISPR".

6 hours ago by gnulinux

Are you seriously arguing in 50 years super rich people won't use this for e.g. cosmetic reasons?

5 hours ago by corpMaverick

Rich people already have easy means for genetic improvements. They just marry people that are more attractive, tall and intelligent.

14 hours ago by koonsolo

Helping people with severe diseases is still far away from creating the perfect humans.

You turning this positive into a negative is distasteful.

12 hours ago by saiya-jin

Road to hell is paved with good intentions. In this case, creating super-humans that lack any weakness, sickness and are just ideal of what can human being be without those is putting them already way above everybody else.

One doesn't need an x-ray vision or flying around to be to have superhuman status.

I understand your optimism because it sounds properly awesome. But we humans always, without exceptions, fuck up everything that is even theoretically fuckable and often even the rest. If you don't see potential for evil with this then I guess you lack a bit of imagination.

For every great discovery to help humanity there is always some powerful idiot thinking how it can we weaponized, used to gain advantage above others, the non-conforming, the unknown, or simply the weak.

10 hours ago by f6v

> we humans always, without exceptions, fuck up everything that is even theoretically fuckable

Don’t mean to intrude, but it reads rather negative. Maybe you should seek help?

14 hours ago by pmlnr

> Helping people with severe diseases is still far away from creating the perfect humans.

Not as far as it looks. Honestly, it looks closer, than real self driving cars.

> You turning this positive into a negative is distasteful.

I'm incredibly happy that we, as humanity, are advancing with science - the mRNA vaccines are also incredible. The part that is not incredible is that we, as society, are in most cases still behave like we did in the stone age: greedy, selfish, narcissistic. Because of this tech that should be used to help those in need is most commonly used to "help" those with enough funds or means.

Cheering for science advancements that are far out of reach for the majority leaves a bitter taste.

EDIT BTW, Gattaca is a temporary time. Once it's passed - one whole generation, so say ~80 years - that world would be wonderful, but that limbo time, when the movie plays out, is the nasty part.

11 hours ago by boxed

> Cheering for science advancements that are far out of reach for the majority leaves a bitter taste.

Yes. Damn that new fancy tech of farming that only the rich can afford!

Seriously. Think about what you're saying for a second. Tech that is only for the rich becomes affordable for the masses faster and faster every year. Computers were for nation states in my parents life time. Today there are computers more powerful than the first computers in cheap toys.

We cheer for tech that only the rich can use now because it will be for the masses soon. Tech that never exists for the rich, will not exist for anyone ever.

Check your logic.

10 hours ago by maxerickson

Gattaca isn't just about the oppression of the natural born.

You cheer for a world full of Anton's, calculating that it isn't possible to make it to the other side, deciding not to try.

18 hours ago by jostmey

I've learned a lot about gene therapy. The immune system is a major bottleneck to wide spread gene therapy. If you modify the genetic makeup of cells in your body, the immune system will recognize the new antigens being presented by these cells and attack. Many gene therapy target point mutations that don't require significant alterations to correct that would alarm the immune system.

10 hours ago by f6v

It’s also that we don’t have organism-scale models of how change in one gene will affect other body functions. We don’t know how to build these kind of models and we don’t have even 1% of the data to do that. Organoids are just emerging, but they aren’t 1:1 representation of what happens in real human.

10 hours ago by amelius

Don't point mutations cause proteins to fold differently? And thus causing the proteins to become globally different rather than locally different?

7 hours ago by jostmey

1. Most point mutations won't result in significant changes, but if we are talking about gene therapy, the specific point mutation probably did effect protein folding or function 2. Proteins in each cell are broken down into unfolded fragments and presented on major histocompatibility complexes as antigen.

20 hours ago by DoreenMichele

“We are motivated to work toward a cure that can be accessible and affordable to patients worldwide,”

Sickle Cell is prevalent in some populations because the gene mutation is protective against malaria. (Probably only beneficial if you have one copy, not two.)

I hope they will keep this in mind and work to eradicate malaria hand-in-hand with trying to eradicate the genes that are protective against it when they look to take it global.

20 hours ago by maxerickson

It's fine if they just figure out how to cure sickle cell anemia. Great even.

No one will force people in areas where malaria is endemic to have sickle cell anemia treated, and a treatment for sickle cell anemia won't slow down treatment/eradication of malaria.

19 hours ago by DoreenMichele

I'm sure no one actually forced mothers in developing countries to buy Nestle baby formula either. Babies died anyway.

There are lots of sources out there. Here are just a couple.



18 hours ago by maxerickson

It's certainly not impossible that governments of African countries would spend thousands of dollars per person to prematurely cure sickle cell anemia, but I think we can say that it's unlikely.

20 hours ago by XorNot

We're a hair's breadth away from using genetic engineering to make the mosquito extinct.

We have the technology (gene drive) but scientists just aren't sure if we should do it.

19 hours ago by BurningFrog

What's talked about is only making the 30-40 of the 3500 mosquito species that carry malaria extinct.

Ecologically, they can normally be replaced by some of the 3460 others.

20 hours ago by DoreenMichele

They are right to have concerns.

There was an island where they used poison to kill all the mosquitoes because it was a big problem. All the mosquitoes dies and then all the things that ate the mosquitoes died.

And then all the things that ate things that ate mosquitoes died. And it went through a few more layers of this, like some modern day version of the Biblical plagues.

That doesn't mean we shouldn't do it. It just means it is correct to not take the decision lightly.

(Unfortunately, I've never found a good write up of this true story on the internet. I read it long ago back when dinosaurs roamed the earth and I had a bright yellow rotary phone and got information printed on dead trees.)

18 hours ago by Jedd

This seems alarmist.

The citation you provided elsewhere (for Sardinia) was for some DDT spraying - which was obviously not targeted exclusively at mosquitoes, and explains why lots of other things died.

Targeting the very small set of mosquito species (that carry malaria) with something that will wipe them out within a few generations (under 12 months) seems tremendously safe, because a) it's a small subset of the total mosquito population, b) you can test this in isolated (eg. island) environments, and c) by the very nature of this, rollback is easy -- once the species has died out locally, if needed you can quickly & safely re-populate with non-modified specimens.

20 hours ago by est31

You don't have to extinguish all mosquito species. It's enough to only target those which can carry diseases. Ideally one would engineer mosquitos to avoid humans because of their smell.

19 hours ago by yardie

Except there are multiple species of mosquito. Only 1 of them is a primary carrier for malaria. And if it disappears another mosquito in the family will replace it.

19 hours ago by Salgat

Do you have a source for this? I linked below the best I could find, which makes no mention of any issues with them wiping it out.


20 hours ago by grishka

The frogs gotta eat something.

19 hours ago by XorNot

The general consensus at the moment is that there's no apparent food chain where mosquitos are the primary source.

20 hours ago by Dig1t

I think about this a lot.

What's to stop some random, non-scientist, group of people from just doing this? Mosquitos are pretty evil..

20 hours ago by maxerickson

If you make a gene drive you are a scientist.

Hopefully whoever decides to just go do it has the sense to only target mosquitoes that preferentially feed on humans. Much less ecosystem impact that way.

19 hours ago by IIAOPSW

"I would die for 2 brothers or 8 cousins". -JBS Haldane


10 hours ago by yarcob

> Probably only beneficial if you have one copy, not two.

One copy of the gene partially protects you from malaria; two copies of the gene make you very sick.

That's why even in Africa only a small portion of the population has the gene. The gene is an evolutionary advantage as long as the prevalence in the population is low. As soon as the frequency of the gene in the population goes up, it becomes a disadvantage because if both you and your partner have the gene your kid has a 25% chance of getting two copies.

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