In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation


Awesome find!

This is unquestionably the most promising study yet in regards to prospective methods of not just treating, but curing, PFS and other diseases suspected of having an epigenetic pathophysiology.

Would like to highlight this statement for emphasis:

As proof-of-concept, we used this technology to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to measurable phenotypes and amelioration of disease symptoms.


Good post.

For everyone else reading who can’t follow the study or don’t have the time to read through it, I’ll offer a quick ELI5.

Imagine gene expression as the volume bar to a track. It needs to be maintained at a certain level for the music to be enjoyable.

A lot of the aforementioned diseases were rectified by using CRISPR to change gene expression. There are certain genes that cause issues, and CRISPR could turn their expression down, while others help, and CRISPR could turn their expression up.

In our case this is relevant because the current idea is that the problems we have could be because of epigenetic changes, something the current studies will hopefully confirm as we cannot think of any other mechanism through which lasting changes have occurred. Once we identify the affected genes and the issues with their expression, once this form of CRISPR is ready for human use, we could use it to rectify the disaster finasteride left behind.

I don’t want to make any promises or get anyone’s expectations up, but I’ve never seen a technology move as fast as CRISPR. The developments are appearing at an exponential rate, and while we might have to suffer for a few more years, I believe it’s only a matter of time before we’re back to our old selves.


Thats a great post that explains the situation very well, im just curious what are the odds it would cause other issues to the body? And if it’s safe, would they charge a price as the big pharmas would lose out on a load of money? thank you

My apologies, I didn’t notice this.

So one of the issues with CRISPR is off target edits. Basically CRISPR edits the wrong gene, and that can lead to issues. The good thing is that efficiency is improving at an exponential rate. Off targets are becoming less and less, with some forms of CRISPR achieving close to 100% efficiency (i.e. no off target edits).

The price is something I can’t comment on. CRISPR kits themselves aren’t very expensive, but it takes someone who’s aware of how to set it up, make the right edits and well, get CRISPR into you. The bright side is that, regulations permitting, when we find a target, we’ll just need to hire someone who knows how to configure the kits and we’re good.

1 Like

Sorry, but i hope not CRISPR is ‘the thing’ we have to wait for. It takes at least 15 years before it’s on the market and then maybe a few years extra for a pfs kit. I hope something else will cure us sooner.

What makes you say 15 years? CRISPR companies have multi billion dollar market caps with barely anything even accepted for review by the FDA. Plus there’s that whole breakthrough therapy thing the FDA is handing out, so that’s another reason to believe it’ll come to market soon.

As far as a PFS kit, we control how soon it comes. The more money we put in consistently, the faster it’ll come. This is something no one really wants to acknowledge, so if you’d like it to come out sooner, set up a reasonably sized recurring donation, or give as much as you can give to the foundation. We underestimate how much power we have.


We are getting ahead of ourselves with the CRISPR talk. We still don’t if there even is a role for CRISPR in PFS and where to apply it even if it where already applicable. We think it might have role, but it’s all speculation before we really know what wrong with us. We first have to understand the condition, before we can think about what to do about it. That’s why supporting the efforts and the foundation is so important. In that regard I agree.

CRISPR is extremely fascinating and provides hope for a lot of conditions. I think it is likely that it can help us in the future, but we don’t know yet. Let’s cross that bridge when we get there.

1 Like

I believe it will be in clinical use before this estimate, as does its co-discoverer. However, @Northern_Star - I agree. It’s not really worth getting ahead of ourselves when the focus must be on what precise molecular changes are causing “PFS”. If we don’t know that then we could have walk in crispr clinics and it wouldn’t do us any favours.

I have quite often seen those not really engaging with the scientific side of PFS say “there wont be a pill for PFS!” to bring discussion to a close, justify an unfounded theory or even reject the pressing need to understand and warn of a condition that has taken and ruined lives. This is not relevant. When we know what is causing it we can begin focusing on how to tackle it, and it’s speculation that specific drug or therapeutic development would be required. Maybe something in development, or soon to be developed could be used. Just in the past fortnight I’ve come across something I’ll be keeping an extremely close eye on. And regarding CRISPR, it’s a fact that when @awor first put effort into organising effort towards understanding what was happening in PFS, few people on earth had heard of it, and its adaptable therapeutic potential was completely unexplored. Now it’s a possibility it could help many in the future. I am as impatient as anyone, but one step a time is the only way to effective progress. Other roads may intersect in the future regarding therapies.


I completely agree with @axolotl. I also want to emphasize that while a cure is what all of us want, there might be therapies that may “only” improve some symptoms. Those of us, for example, who like me largely suffer from symptoms that are probably related to altered neurosteroid levels, may find some relief in analogs of allopregnanolone that are currently under development. We don’t know yet, but it’s certainly possible and one of the many angles that provide some hope.

So, the Baylor study is still outstanding, which will hopefully provide breakthrough insights into our condition. Melcangi is conducting further studies. We have the aforementioned analogs in advanced clinical trails (!) which may provide relief for some of us, and then there is the general scientific progress that may provide new medications, CRISPR therapies or simply new research alleys to explore. There is a lot going on. While our situation is difficult, there is no reason to give up. We haven’t reached a dead-end yet. In fact, I’d say we are just getting started. So let’s be productive and make progress.