CRISPR takes important step toward silencing Down syndrome’s extra chromosome

https://medicalxpress.com/news/2026-04-crispr-bold-silencing-syndrome-extra.html

by amichail • 3 months ago

225 91 3 months ago

This is very clever - the X chromosome has a mechanism to shut itself down (which makes sense; otherwise cells in women would have twice as many gene products from the X chromosome as cells from men).

The linked research report[1] uses that mechanism, Xist, to shutdown chromosome 21, the extra chromosome whose presence causes Down syndrome. In its present form, it would need to be optimized for each potential patient and is unlikely to be used as a treatment paradigm, but the biological approach is clever.

[1] https://www.pnas.org/doi/10.1073/pnas.2517953123

sheept• 3 months ago

the X chromosome has a mechanism to shut itself down (which makes sense; otherwise cells in women would have twice as many gene products from the X chromosome as cells from men).

You can see this visually because not the same X chromosome is deactivated in all cells: it's what gives calico cats their color (almost all of them are female).

dreamcompiler2• 3 months ago

Human women have stripey skin too, but you can't see it under normal light because unlike cats, skin tone in humans is not controlled by the X chromosome.

https://www.youtube.com/watch?v=BD6h-wDj7bw&t=225s

Symmetry2• 3 months ago

Likewise humans with heterochromatic eyes are generally women.

shevy-java4• 3 months ago

And how do they ensure that only one X chromosome is inactivated? All three X chromosomes are, for the most part, equal, neglecting differences between father and mother X chromosome and changes during meiosis.

samus2• 3 months ago

Presumably by targeting them toward these differences.

memonkey• 3 months ago

I am slightly reminded of Gattaca, the story of which is that certain people are discriminated based on their DNA. Society is built, in general, excluding certain people due to their disabilities. Whether or not a blind person can find meaning or enjoy life has road blocks but is not impossible. Science can provide technologies to potentially improve people's lives -- cochlear implants for those with hearing loss, for example. There are ongoing philosophical discussions of whether or not these technologies and scientific discoveries are actually harming or helping those with these disabilities and the broader discussion of 'normalizing' society at large (I don't want to use the term eugenics).

colechristensen2• 3 months ago

There are arguments about various "conditions" being diseases or not, Down Syndrome really isn't one of them.

hgoel2• 3 months ago

Recognizing that certain mutations very blatantly reduce a person's quality of life and making it possible to revert those mutations does not require treating the people who have not had those mutations reverted as lesser.

Thinking of them as lesser leads to a society that prefers to drag each other down instead of lifting each other up.

TurdF3rguson2• 3 months ago

I don't know about this argument because they seem a lot happier than I am.

That's not to say that it's unreasonable to value intelligence over happiness, but framing it as quality of life seems off.

wqaatwt• 3 months ago

That’s still eugenics, though. Except this time it’s not pseudoscience.

Metacelsus• 3 months ago

If they're going to all that effort to make allele-specific guides why not just cut out the centromere and eliminate the chromosome entirely? This seems like an overly complicated solution.

russdill• 3 months ago

My understanding is that crispr is less like a scalpel and more like a chainsaw. Great care just be taken to avoid introducing cancer causing mutations.

colechristensen2• 3 months ago

I wouldn't characterize it like that. It makes mistakes. It's a scalpel in shaky hands. When it works correctly it is very precise but just not 100% reliably.

in vitro there are various techniques where you use crispr on a cell line and then purify it by killing off the cells with errors and only then implant them

in vivo... well there are errors and among other effects are potential cancer

irjustin• 3 months ago

I wondered the same thing and according to Gemini a chromosome is massive vs a few genes. Cutting it out with crispr is possible, but it's too big of a change and would lead to cell death rendering whatever change either useless or kills the host given the possible stage this treatment could be delivered at.

samus2• 3 months ago

Since the presence of that chromosome causes problems in an organism that functions normally with just two of these chromosomes, the change is actually not that big. And the therapy might also not be intended for adults or even children - most of the developmental impediments have already happened at that stage, and neither cutting out the extra chromosome or silencing it will fix this up.

ceejayoz4• 3 months ago

Now ask Gemini what chromosomal anomaly causes Downs. It will likely be enlightening.

shevy-java4• 3 months ago

But this has the same problem as before - how can you ensure that only one X-chromosome is killed off? Or at the least one?

shevy-java4• 3 months ago

After skimming through, one obvious question follows:

How can they ensure that (only) one out of three chromosomes only, have XIST integrated? (I assume they can target these three chromosomes due to the CRISPR RNA.)

So down syndrome is trisomy 21, aka three chromosomes 21. Say you have to modify a billion cells, just to give a number. Well, how can you ensure that all those have one XIST gene that is also active (otherwise it would be pointless; XIST produces a RNA which in turn silences the X chromosome by coating it)? Inserting new genes is nothing new, that is already ancient technology at this point in time.

https://en.wikipedia.org/wiki/XIST

kriro• 3 months ago

Great achievement. Sometimes I imagine a world where the LLM-money, will and time was funneled into more aggressive CRISPR research and medical advances in general. If I want to go full sci-fi I even imagine cloning.

Cthulhu_2• 3 months ago

Cloning isn't even sci-fi or imaginary, just morally questionable and... variably legal (https://en.wikipedia.org/wiki/Human_cloning#Legal_status_of_...). Same goes for gene editing / designer babies / eugenics, which overlaps strongly with the subjects in this discussion.

akramachamarei• 3 months ago

Let's not conflate eugenics with gene editing or "designer babies." On the contrary, there is little overlap between eugenics and any of the three other topics, but for the vaguest vernacular sense.

voidUpdate5• 3 months ago

I have very conflicted feelings about this sort of thing. On the one hand, Down's syndrome can make life very hard, for both the person with it, and their carers and the people around them. I can imagine that some people would have preferred it if they were able to "cure" it. I've often felt in the past that I would have preferred to have been born without autism and ADHD, and while I've been coping a little better with it nowadays, it definitely had a large impact on my childhood, and I know my parents struggled with it a lot.

On the other hand, this feels a bit like eugenics, and a slippery slope towards designer babies where you can pick and choose their attributes. I'm of the opinion that we should embrace the full diversity of human life, and if you can just cut out the parts of your children you don't like, that feels quite iffy to me

c048• 3 months ago

The full diversity of life sounds wonderful, as long as you're not the one suffering painful, disfiguring or crippling conditions.

voidUpdate5• 3 months ago

I am the one suffering from multiple of those conditions

exe342• 3 months ago

I've always thought we should maintain a list of people like you. Every time we cure something, like blindness in one person, one of you gets picked and your eyes get poked out. That way the total amount of suffering will be conserved, but those who think that's necessary get to be the ones who pay the price for their beliefs.

voidUpdate5• 3 months ago

In the first half of my comment, I explained that I don't think people should suffer. I'm just also aware that if everyone can pick their child's attributes, it could lead to a nation of blond-hair, blue-eyes kids

dpiers• 3 months ago

We already live in a world where parents decide whether or not a child with Down Syndrome will be born.

60-90% of prenatal diagnoses in the US result in an elective termination. The number is nearly 100% in Iceland and some other Nordic countries. Unlike autism or ADHD, we have a very clear understanding of exactly what causes Down Syndrome and now potentially how to correct it. A treatment like this is no different from correcting a congenital heart defect - it gives a baby a chance at normal, healthy development.

Qem• 3 months ago

it gives a baby a chance at normal, healthy development.

And a chance of not being killed in utero. Abortion for Down is sad, because despite cognitive impairment and health complications, their lifespans are long, and emotional development is quite spared by the syndrome. They can be very affectionate and sociable, despite the impairment. Abortion for them feels like death penalty for being dumb.

rob74• 3 months ago

Ok, that just leaves us with another quandary: deciding whether to terminate the pregnancy (hoping that the parents will get a "normal" child on the next try), or let the child be born and use this (no doubt very expensive) therapy to cure it? Not sure medical insurers would cover it? Maybe Christian anti-abortion groups will donate money for this therapy to parents who choose to have a child with Down syndrome? OTOH, they might consider that interfering with God's will to have an impaired child be born?

mkesper• 3 months ago

You got to weigh this against abortions for unborn children diagnosed (maybe even wrongly, the tests are really not that exact) with Down's syndrome. The slippery slope already began a long time ago probably.

robertjpayne• 3 months ago

By week 20 there is practically no chance you're not going to know if you're carrying a baby with downs or not unless you refuse all the modern screening/tests available.

NIPT tests can be done at week 8 and give a very high indicator that can be followed up with close monitoring/invasive tests at week 14-15 that give a 99% accuracy. That's hardly "are really not that exact".

lofaszvanitt• 3 months ago

What are you talking about? WHAT are you talking about?

fainpul• 3 months ago

I understand the concerns, but some things just make life much harder. I would definitely want to spare my child from living with autism, ADHD and certainly Down syndrome, given the choice. It's not like we're talking about choosing eye color, height or gender here.

Tade0• 3 months ago

Not to downplay your situation, but this is Down's syndrome we're talking about, so a whole menagerie of both physical and mental conditions, including, but not limited to: higher risk of epilepsy and heart failure, aside from almost universal infertility in men.

It's a serious disability even today decreasing life expectancy by 10-15 years.

One may have different opinions regarding the quality of life of these people while they're alive, but I think we can agree that 60 years is a short lifespan for a human.

EDIT: also main point of eugenics, which seems to be not widely understood, was that the state would decide both what kind of children are born and who gets to have them. It was not unheard of to take sufficiently "aryan"-looking newborns from their "inferior race" parents and give them to "master race" adoptive parents.

This lack of agency on part of biological parents is a core tenet of eugenics.

poulpy123• 3 months ago

Of course gene editing has the potential to go very wrong, and will almost certainly go very wrong. But trisomy 31 is a well defined genetic defect with heavy consequences on the person having it and his or her entourage and there is no ethics preventing to correct the issue even if the technology used can be also used for nefarious means. It would be like not using dynamite for freeing miners in a collapsing mine because in the future there will be bombs made from dynamite targeting children.

igleria• 3 months ago

What would be the difference between curing a fetus versus a newborn? Isn't editing out the bad gene better than just aborting gestation? For the person gestating too, since going through an abortion is psychologically damaging

azan_2• 3 months ago

I'm sorry but if elimination of crippling disease sounds like eugenics to you, then you should deeply think about your moral compass. Comparing autism (I guess some mild form since you put it next to ADHD) and ADHD to Down's syndrome shows that you are completely clueless. I'm sorry for the harsh tone but your comment is absolutely awful and has zero empathy towards people (and their caretakers) suffering from condition much worse than what you are going through.

ceejayoz4• 3 months ago

For where this gets complex, you can look at the Deaf community.

Crippling disease? Or normal variation in humanity? There's significant debate, and a lot of Deaf people really bristle at the idea of eliminating their identity.

throwatdem123112• 3 months ago

Natural Selection might as well be called Natural Eugenics.

I have people in my family with Downs. It made the early pregnancies for every one of my children a terrifying ordeal. Luckily my children were all born perfectly healthy.

I love my family members with it, but their lives have been so much more difficult than they needed to be. It’s not just massively difficult for the disabled, it financially ruined their parents and their care is also a massive tax burden on the community.

If we can eliminate a crippling disease by “just” turning off a gene we should absolutely do it. The alternative is aborting them as soon as it is detected, and even then it isn’t always caught in-utero.

I have worked with people will all sorts of disabilities my entire life. I can confidently say that if I asked any of my blind or deaf colleagues that if they could take a simple gene therapy so they could see/hear again that they would do it without hesitation. Why would Down Syndrome be any different?

I can’t think of a single valid argument against it other than “eugenics bad”. We aren’t talking about Nazi-era human experimentation here.

api2• 3 months ago

As I said in another comment, eugenics is state authoritarian control of reproduction and fertility (with the extreme version being genocide).

There are very few people with a disability who wouldn’t want it to have been prevented or cured. “A healthy man has many dreams. A sick man has only one.”

thinkingtoilet• 3 months ago

Ignore commenters trashing you. It is very ok to have conflicted feelings about something like this. I think this is a good thing but understand where you're coming from. Let me tell you my family's story.

I have a brother with developmental disabilities. Not Down Syndrome, but something similar. He (and I) were lucky enough to be born into an upper-middle class family where my brother went to a school where people were kind to him and where services were available. Despite everything going about as well as it could, it still is a major tax on my family. Constant fund-raising for the home he's living in. Major medical problems through out his life. Things like that. When I agreed to kids with my wife it was on the condition that we do genetic testing and abort the fetus if there was an issue.

My mother has invested her life into this child and loves him more than anything. One day we were talking about death and I casually said something along the lines of "as long as I don't see you at <brother's name> funeral" I'll be ok. Implying she should die first so she doesn't have to deal with the sadness of seeing him die. She then said that she wanted my brother to die first. I was stunned. I asked why. She said she wanted to know he was taken care of. It completely floored me. People with Down's (and similar disabilities) can bring so much joy into this world. They can live very happy lives. I understand how it can be hard for people who don't have my experience to feel like you're feeling. However, I wouldn't wish it on anyone. And I think it's a good thing for society to stop babies being born that are so disabled they'll never be able to take care of themselves.

Just my two cents.

TeMPOraL• 3 months ago

On the other hand, this feels a bit like eugenics, and a slippery slope towards designer babies where you can pick and choose their attributes.

We can discuss pros and cons of freedom of choice of genetics for your children (an opposite spin on the same idea as calling it "designer babies"), but eugenics is a thought-terminating cliche at this point. There's whole space of useful genetics-based treatments and interventions that do not imply involuntary sterilization of people one group deems lesser.

api2• 3 months ago

The best thing to do with the term eugenics is to define it specifically as authoritarian control of reproduction.

Voluntary acts aren’t eugenics, otherwise you get absurd things like free choice of mates being eugenics because you are choosing, or any medical treatment being eugenics if it touches genetics or reproduction. Eugenics should be defined as meaning only authoritarian (directly or via state backed “social engineering”) forms.

ben_w• 3 months ago

While I agree with you that it's a thought-terminating cliche, I would caution that humans have historically been very inaccurate with knowing what traits specifically are good vs. bad, while also very strong on enforcement of ingroup/outgroup and purity dynamics.

We could all be hyper-muscular (from that Myostatin gene) and have tetra-chromatic vision*, but that leads to the joke about how "in the future there will be three genders: kpop, furry, and tank", where kpop represents normative beauty standards, furry represents self-expression, and tank represents hyper-optimising for niche goals like being strong.

On the more near-term impacts, before we're ready for me to get turned into an anthro-wolf, if we all end up with our genomes subject to regular updates like our software currently is, some of us are inevitably going to face our cells getting bricked while we're still made of them.

* I don't know how that works so here's the wikipedia page: https://en.wikipedia.org/wiki/Tetrachromacy#Humans

iLoveOncall• 3 months ago

Congratulations, you just won the trophy for most privileged comment on the web!

equinox6380• 3 months ago

hgoel 2 minutes ago | parent | context | on: CRISPR takes important step toward silencing Down ...

I chose to call it quality of life because I don't think that simply being happy is enough to have quality of life, but I don't agree that it's about valuing intelligence over happiness. It's a condition they, and their family, have to live with their entire life. You can't really be permanently sad about a condition you have literally been born with and can't expect to change.

Meanwhile, there are conditions that significantly decrease quality of life even though one's intelligence is unaffected. I think the factor is better described as choice. There are a large number of things a person with Downs just does not have the choice to do differently.

CRISPR takes important step toward silencing Down syndrome’s extra chromosome

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