This Guy Says He’s The First Person To Attempt Editing His Dna With Crispr

[Jonnyyy]

Right, but those are only the SNPs that reached genome-wide significance in that particular study. Boyle, Yang, and Pritchard estimate that ~100,000 SNPs contribute to complex traits, but that most have tiny effects and escape detection.



So there could be loads of SNPs with odds ratios like 1.002 contributing to A.G.A heritability, but Hagenaars et al. didn't have the power to go below ~1.03 with "only" 52,000 people.



In terms of p-value that's always true (at least in Europeans, since the risk allele for the top hit near AR is fixed in East Asians). In terms of effect size, that's usually true as well, but the largest effect sizes in Hagenaars et al.'s dataset were in rare variants around RSPO2 on Chromosome 8, with ORs up to 6.12 reaching genome-wide significance.

(I added the p < 5e-8?, |Beta|, and OR columns into the summary data)

View attachment 66383

The region around AR on the X chromosome goes up to 1.79.

View attachment 66384

Variants around the SRD5A2 (5-alpha reductase type II) gene on Chr2 aren't far behind AR.

View attachment 66385

But the comparison between the AR and RSPO2 or SRD5A2 regions isn't fair, since they didn't have imputed data for the X chromosome. Maybe AR would win in OR too with imputed data...And those rare variants must have huge error bars as well.



What would be the advantage in doing that instead of silencing AR totally in scalp dermal papilla cells?

And another question: Do you think individual genome sequencing and editing might help with reversal and not just maintenance?

I think editing of the genes would have the same effect that medicine does, medicine basically tries to silence those genes but you have to take it everyday. With gene editing it would probably reverse hairloss / maintain depending on how many genes that relate to baldness you decide to eliminate. Are all the 250+ genes you guys mentioned in every single bald/balding guy? If you could compare the genes with those that bald young and those that bald late I'm sure you can see which genes are more prominent for balding and tackle those.

 

[bags]

I'm more interested in the CRISPR kit that's gunna give all of us 12 inch hogs lmaoo. JK in big enough, I'd rather have a full flush head of hair lol

 

[GodisnotBald]

This guys worked at the NASA , is a PhD from a popular university; its neuronal connections seems decent enough to bring a breakthrough tech in the market one day;

For those interesting in the economic relevancy of a CRISPR kit to treat genetic disorders such as alopecia for big pharma companies in the future; they could patent the process and work directly with private hospitals to sell such kits at huge price (everybody here would pay 10.000 to come back to Norwood 0 / 0.5 / 1) for minimal costs

Crossed fingers

 

[Jonnyyy]

This guys worked at the NASA , is a PhD from a popular university; its neuronal connections seems decent enough to bring a breakthrough tech in the market one day;

For those interesting in the economic relevancy of a CRISPR kit to treat genetic disorders such as alopecia for big pharma companies in the future; they could patent the process and work directly with private hospitals to sell such kits at huge price (everybody here would pay 10.000 to come back to Norwood 0 / 0.5 / 1) for minimal costs

Crossed fingers

I'm sure if this guy wanted to he could create a kit in under a year that would remove most balding genes but you'd probably have to inject yourself with that sh*t everyday for it to work as you saw where he was injecting himself multiple times trying to grow muscle lol.

 

[Keisi92]

I still think this is a concotion for disaster, plus has anybody ever thought about the philosophical problems this brings? Or the changes it might bring to you?
Character and personality are made groing up mostly, but there are still things we inherit from our genes, wouldnt changing them change us too in a way? I mean i wouldnt want to have a full head if hair if i would have a chance of not being myself again.

Dont want to be a bummer,but every gene could very well have more than one function or could have unexpected complications for changing it, I know that docs some times like to say that they are close, but if it took them this many years and still have not found a cure to hairloss, using crispr for gene modification looks very far away in the future for me.

 

[kawnshawn]

Bacteria and virus constantly modify your genes when they infect you, that's one of the reasons DNA suffers damage as we age (besides the accuracy of the iteration process that has a margin of error as cells divide). This would be doing the same thing, only fixing something that was broken that should never be broken.

Also, CRISPR is being used for a variety of applications, including curing some types of blindness today. This is not the future, this is today. The cure for Hairloss, via the CRISPR method is significantly more within reach than any drug cocktail meant to suppress genes (rather than modify) with untold side effects for purposes of treating (rather than curing) the condition.

With CRISPR, you skip the treatments and get the cure. It's possible, and it is possible in the short term as well and outside of regulations (so far), so it's not unreasonable to pursue.

I can guarantee you that CRISPR for hair loss is nowhere within reach. Gene editing is still very much in its infancy and is a controversial field. There is absolutely 100% zero chance that the average Joe will be able to go out and edit his genes. The FDA will come down hard on any person or business selling "kits" to edit their genes and will regulate strictly like it does when it comes to something as serious as this. If a company wants to market gene editing for hair loss it will have to go through the same trials as other health and medical companies which will take years and millions of dollars. Not trying to be a downer but we gotta be realstic.

 

[Jonnyyy]

I can guarantee you that CRISPR technology is within reach now, and much more so than when the FDA starts regulating it. You believe what you want, and I'll believe what I want - just because you don't think it can happen doesn't phase me one bit. I know quite a lot about CRISPR, and if I had the time I'd get a second degree in bio engineering so I could solve this problem myself. It would be just like hacking code, not that challenging.

Do it then, youd become rich as f*** hopefully before the FDA regulates it, you would have a lot of incentives, money and your hair back.

 

[BaldyBalderBald]

Well-writen interesting and approachable article here, explaining to rookies like us current advantages and flaws of this tech in his current state
The gene editor CRISPR won’t fully fix sick people anytime soon. Here’s why
http://www.sciencemag.org/news/2016...fully-fix-sick-people-anytime-soon-here-s-why

Bottom Line
Gene therapists remain excited by CRISPR, in part because it could tackle many more inherited diseases than can be treated with gene transfer. Among them are certain immune diseases where the amount of the repaired protein must be precisely controlled. In other cases, such as sickle cell disease, patients won’t get completely well unless a defective protein is no longer made by their cells, so just adding a gene isn’t enough. “It opens up a lot of diseases to gene therapy because gene addition wasn’t going to work,” Dunbar says.

After more than 2 decades of seeing their field through ups and downs, veterans of the gene therapy field are wary of raising expectations about CRISPR for treating diseases. “Whenever there’s a new technology, there’s a huge amount of excitement and everybody thinks it will be ready tomorrow to cure patients,” says gene therapy researcher Mark Kay of Stanford University in Palo Alto, California. “It’s going to take some time.”

Last phrase is the biggest bummer here.We pretty much all know around here what "It's going to take some time" means in medicine, especially where you are messing around with human DNA.

I'm no expert, far from it, but sh*t guys, you know the drill.

 

[Jonnyyy]

Well-writen interesting and approachable article here, explaining to rookies like us current advantages and flaws of this tech in his current state
The gene editor CRISPR won’t fully fix sick people anytime soon. Here’s why
http://www.sciencemag.org/news/2016...fully-fix-sick-people-anytime-soon-here-s-why

Bottom Line
Gene therapists remain excited by CRISPR, in part because it could tackle many more inherited diseases than can be treated with gene transfer. Among them are certain immune diseases where the amount of the repaired protein must be precisely controlled. In other cases, such as sickle cell disease, patients won’t get completely well unless a defective protein is no longer made by their cells, so just adding a gene isn’t enough. “It opens up a lot of diseases to gene therapy because gene addition wasn’t going to work,” Dunbar says.

After more than 2 decades of seeing their field through ups and downs, veterans of the gene therapy field are wary of raising expectations about CRISPR for treating diseases. “Whenever there’s a new technology, there’s a huge amount of excitement and everybody thinks it will be ready tomorrow to cure patients,” says gene therapy researcher Mark Kay of Stanford University in Palo Alto, California. “It’s going to take some time.”

Last phrase is the biggest bummer here.We pretty much all know around here what "It's going to take some time" means in medicine, especially where you are messing around with human DNA.

I'm no expert, far from it, but sh*t guys, you know the drill.

THris sh*t made me happy, I'm sure in 20-30 years this will be capable of curing us.

 

[BaldyBalderBald]

THris sh*t made me happy, I'm sure in 20-30 years this will be capable of curing us.

Yeah well, i'll be 50-60 by then, in the meantime, gotta still pop this finasteride pill.
I hope effective treatments with less sides will come before counting on this.

 

[Jonnyyy]

Yeah well, i'll be 50-60 by then, in the meantime, gotta still pop this finasteride pill.
I hope effective treatments with less sides will come before counting on this.

Kind of doubt it, looking through the forums I see the same sh*t 12-13 years ago people ranting about all sorts of companies coming with products and look now "in 1 year we'll have our first non finasteride with no side effects" it's not gonna happen I don't think these companies are gonna keep delaying until we're old af and have no hair left.

 

[lemoncloak]

I'm not trying to bring you down here, but the opposite.I've been lurking this forum, blogs like HL2020 and so on for more than 15 years now, jumping and falling from hype train with sh*t amounts of various cure promises.

You're still young, and watching you spending that much of energy, creating like 5 threads a week, and gather as much hope as you can on this.Well sh*t, this breaks my heart, i'm seeing myself here.

If i can avoid you frustration and disappointment, i feel like i must do it.

And don't get me wrong, this kind of technology could potentially lead to the final cure, but in how many years ? You could be grandpa by then.
I know this sh*t hurts, started balding at 15 in 2001, and f*** i was lucky some working treatments were already out, even if these are f*****g horrible.

Don't worry m8. Back then, only intercytex/aderans were on the right path and they failed because of freakin financial problems. Just because there was a lot of research then and now doesn't mean it's the same thing. I hope your sons at least will never have to worry about hair loss.

@d3nt3dsh0v3l sorry for not responding to your question about AP muscles, was busy with ball surgery I actually hadn't realised Tsuji didn't grow new muscles and nerves but made connections to the old ones until you pointed it out. I can see the possible problem there, but it's probably not important cause these muscles are vestigial(?) and only useful for piloerection. Worst case, I think we can live without goosebumps on our scalps. The fact that hairs tend to align with surrounding structures like those is probably because they all get aligned towards those pcp protein signals we were talking about in the follica thread, not because the muscles themselves define hair direction.

 

[moxsom]

What would be the advantage in doing that instead of silencing AR totally in scalp dermal papilla cells?

I have worked in genetics or done genetic research for the last 6 or so years. Admittedly while I have certainly read sparingly about siRNAs I only have heard about them in real life as a research tool. Their clinical utility has not really come to fruition. When I moved over to the clinical world in genetics 3 years ago I have not heard a peep about siRNAs. On the other hand I'm able to attend weekly talks on research clinicians getting super excited about CRISPR. I have never seen this level of excitement for a gene editing tool.

To further dig into your question I think this paper does a good job. They state the following "Many of the genetic diseases will benefit from gene therapy through stable gene editing. As RNAi is unable to either stably introduce gene segments/mutations or induce activation of genes, CRISPR/Cas9 system will be the method of choice for such gene therapy applications. Because CRISPR based gene editing is heritable, technically, one will have to introduce the genomic changes into host cells only a single time, and the physiological effect might last as long as the targeted cells are viable, or will be inherited to daughter cells in the case of dividing cells. In contrast to CRISPR/Cas9, in vivo application of RNAi is limited only to the instances in which the expression of genes has to be suppressed post-transcriptionally."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813155/

I think the dividing cells part here is big. . We know that dermal papilla (DP) cells not only regulate hair follicle development and growth, but they are also thought to be a reservoir of multi-potent stem cells. One change to your DP androgen receptors and bam, it's permanent for the rest of your life.

And another question: Do you think individual genome sequencing and editing might help with reversal and not just maintenance?

Good question. This is much easier to answer for monogenic diseases such as duchenne muscular dystorphy (DMD) where there is a protein disruption event due to a mutation. When this broken gene has been fixed in mice and dogs via CRISPR, they have seen a reversal of symptoms. I believe this reversal will happen with many monogenic diseases but this is of course very dependent on what damage has been done and what proteins were affected. In mice with Huntington's Disease which can cause a build up of nasty proteins in the brain, they even saw the proteins disappear and the mice showed signs of improvement (https://www.jci.org/articles/view/92087).

Now onto these f*****g polygenic diseases like hair loss. As you had previously mentioned there are MANY small affect alleles that are contributing to baldness but the hardest part about this is that many of these do not correlate to protein changes directly. Many of these are in non-coding regions and while they may have some effect on promoters or splice sites, it's REALLY hard to tell.

But say we find you have some larger effect allele like (rs9282858; P=8.9 × 10−18 in https://www.nature.com/articles/ncomms14694) which causes a missense variant (c.145G>A; p.Ala49Thr) in SRD5A2. This modified 5-alpha reductase gene causes WAY more 5 alpha reductase, which may be a main player in YOUR baldness. So f*** that, let's CRISPR that right out.

This might happen for a few more large effect alleles as well, we'll ignore all those small 1.02 OR effect alleles because we'd be here all day and that may be insanity.

Will this reverse hair loss? Hard to say. Maybe. One thing that does give me hope is very strong anti-androgenic treatments reversing hair loss, but I suppose that isn't really the case here. It does give me hope that the DP stem cells can be rejuvenated though.

 

[Jonnyyy]

I have worked in genetics or done genetic research for the last 6 or so years. Admittedly while I have certainly read sparingly about siRNAs I only have heard about them in real life as a research tool. Their clinical utility has not really come to fruition. When I moved over to the clinical world in genetics 3 years ago I have not heard a peep about siRNAs. On the other hand I'm able to attend weekly talks on research clinicians getting super excited about CRISPR. I have never seen this level of excitement for a gene editing tool.

To further dig into your question I think this paper does a good job. They state the following "Many of the genetic diseases will benefit from gene therapy through stable gene editing. As RNAi is unable to either stably introduce gene segments/mutations or induce activation of genes, CRISPR/Cas9 system will be the method of choice for such gene therapy applications. Because CRISPR based gene editing is heritable, technically, one will have to introduce the genomic changes into host cells only a single time, and the physiological effect might last as long as the targeted cells are viable, or will be inherited to daughter cells in the case of dividing cells. In contrast to CRISPR/Cas9, in vivo application of RNAi is limited only to the instances in which the expression of genes has to be suppressed post-transcriptionally."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4813155/

I think the dividing cells part here is big. . We know that dermal papilla (DP) cells not only regulate hair follicle development and growth, but they are also thought to be a reservoir of multi-potent stem cells. One change to your DP androgen receptors and bam, it's permanent for the rest of your life.



Good question. This is much easier to answer for monogenic diseases such as duchenne muscular dystorphy (DMD) where there is a protein disruption event due to a mutation. When this broken gene has been fixed in mice and dogs via CRISPR, they have seen a reversal of symptoms. I believe this reversal will happen with many monogenic diseases but this is of course very dependent on what damage has been done and what proteins were affected. In mice with Huntington's Disease which can cause a build up of nasty proteins in the brain, they even saw the proteins disappear and the mice showed signs of improvement (https://www.jci.org/articles/view/92087).

Now onto these f*****g polygenic diseases like hair loss. As you had previously mentioned there are MANY small affect alleles that are contributing to baldness but the hardest part about this is that many of these do not correlate to protein changes directly. Many of these are in non-coding regions and while they may have some effect on promoters or splice sites, it's REALLY hard to tell.

But say we find you have some larger effect allele like (rs9282858; P=8.9 × 10−18 in https://www.nature.com/articles/ncomms14694) which causes a missense variant (c.145G>A; p.Ala49Thr) in SRD5A2. This modified 5-alpha reductase gene causes WAY more 5 alpha reductase, which may be a main player in YOUR baldness. So f*** that, let's CRISPR that right out.

This might happen for a few more large effect alleles as well, we'll ignore all those small 1.02 OR affect alleles because we'd be here all day and that may be insanity.

Will this reverse hair loss? Hard to say. Maybe. One thing that does give me hope is very strong anti-androgenic treatments reversing hair loss, but I suppose that isn't really the case here. It does give me hope that the DP stem cells can be rejuvenated though.

How long do you think before this is possible to do on humans? And if already possible I'm sure it'll be another 10 years before it's actually done and available in clinics and sh*t.

 

[OFXMBLD]

How long do you think before this is possible to do on humans? And if already possible I'm sure it'll be another 10 years before it's actually done and available in clinics and sh*t.

30 years, unless artificial neural networks approach the singularity and we can direct their near infinite power for genetics engineering without ending humanity. That's the foolish way of thinking someone with ultimate power would be benevolent and use it to put hair on our heads instead of simply wiping everyone out and enslaving whom they please.

 

[BaldyBalderBald]

30 years, unless artificial neural networks approach the singularity and we can direct their near infinite power for genetics engineering without ending humanity. That's the foolish way of thinking someone with ultimate power would be benevolent and use it to put hair on our heads instead of simply wiping everyone out and enslaving whom they please.

lol wat ?

 

[RegenWaiting]

300 genetic markers have been already identified and potentially linked to baldness.Final list, if it ever comes, will be even longer.

300 genes that could contribute to male pattern baldness – most of which come from the X chromosome, good luck with that biohackers, editing that much genes they will end up looking like a Chronenberg, with hair tho

View attachment 66378

More practical approach would be to target(silence) the AR in the balding region of the scalp.

I get your point, though...

 

[Jonnyyy]

For those who don't think gene therapy is within reach, read this article that was posted today:
https://gizmodo.com/this-guy-just-injected-himself-with-a-diy-hiv-treatment-1819659724

Three biohacker friends created an experimental gene therapy treatment for HIV and this guy just injected himself. I'm sorry but the biohacker movement is real, and it is within reach. If they can do this for HIV, we can do it for baldness.

Anyway we can contact these fuckers?

 

[Mage]

Anyway we can contact these fuckers?

Flaunt around some money and they will come.

 

[Jonnyyy]

Flaunt around some money and they will come.

No offense to anybody that has aids lol but this is a much bigger market, not sure how all these Biohackers are missing it.