Why don't we silence the AR gene?

[Boba155]

Besides the obvious *very* important issue of tissue specificity, seems quite easy. It's already been done in rats.

Simply synthesize siRNA that is complementary with the AR gene or with it's transcripted mRNA. Now just deliver it into the organism.

This will either knockdown the actual AR gene permanently, or will degrade the mRNA that it produces.

The result? No androgen receptors.

Voila. You have hair without androgen receptors, and thus nothing for testosterone and DHT to bind to. No male pattern baldness for you.


Seems we just need an EXTREMELY exclusive tissue delivery system. Anyone?

 

[Boba155]

Jesus this forum is slow, no wonder we haven't found a cure yet.

 

[Boba155]

Believe it or not, I have read that thread.

However, this makes no difference. You can't upregulate something that does not exist.

Take out the gene coding for androgen receptors, and they simply will not be produced. Destroy the remaining receptors with a drug like ASC-J19, and voila!

Your hair is now completely empty of androgen receptors.


The only problem is the issue of tissue specificity. While no androgen receptors would be excellent in hair follicles, it would be devastating in the prostate or testes. Thus, this cannot be administered systemically.

The only way I can think of are ultra-selective liposomes, but would they enter the bloodstream through the hair follicle?

Any tips?

 

[Boba155]

Any ideas for MY thread?

And no finasteride, my job in the lab isn't for hairloss. Hairloss is my own private vendetta.

 

[Rabid]

I believe hair follicle RNA, like that of any other tissue, have unique "non-coding" nucleotide segments in proximity to the AR gene, or pretty much any gene, that can be replicated and appended as "homing" strands to allow preferential selectivity for the follicular AR receptor gene strand.

 

[Boba155]

Rabid,

Wouldn't the AR gene in other tissue, i.e. the testicles and prostate, have the same sequence? That's the reason I'm afraid to inject the siRNA: I thought that the effects would be systemic. Remember, all of our somatic cells have identical DNA.

Does each tissue type have a specific sequence before and after the gene? If so, this could easily be the cure to male pattern baldness.

 

[Rabid]

Rabid,

Wouldn't the AR gene in other tissue, i.e. the testicles and prostate, have the same sequence? That's the reason I'm afraid to inject the siRNA: I thought that the effects would be systemic. Remember, all of our somatic cells have identical DNA.

Yes, but doesn't really matter...

Does each tissue type have a specific sequence before and after the gene? If so, this could easily be the cure to male pattern baldness

Yes, I'm' reasonably sure of this from a factual as well as purely logical standpoint. Worst case it might come down to heavy super-computing analysis to seek out these sequences, but they're there. Think about it. What allows your prostate cells to resemble one another so well yet look so different from hair follicle cells? They all have similar enough RNA to each other, yet distinct enough to form tissue easily distinguishable from the rest of the body. That kind of basic logic forms the basis of the most advanced bio-engineering.

Would the technique have to be 100"% fail-safe? I don't know. Would it be safe enough if not every single follicle AR was destroyed or if an occasional non-follicle AR showed up missing? This would definitely not be devoid of errors.

 

[Boba155]

Rabid, this still does not change the fact that every one of our cells, since they have identical DNA, would have those same noncoding nucleotide sequences upstream of the AR gene. Thus. even if you used those as homing sequences, the AR gene in your testes and prostate would be affected as well.

 

[Rabid]

True, but what about the RNA? That's where only the tissue-specific stuff is.

 

[Boba155]

I was under the impression that introns/exons of RNA are not tissue specific. Am I wrong?

And besides, if we are talking about RNA now, we are simply talking about a treatment, not a cure. Just like Finastride and 5a-2 enzyme, no doubt some RNA would not get destroyed by siRNA.

To truly cure this disease, we need to address and destroy it's source: the DNA gene.

 

[Rabid]

Is this any use? Keep in mind it's from 1982...

http://www.jstor.org/pss/12642


Targeting tissue-specific DNA seems difficult because as you said there is no tissue specific DNA. With RNA that's what really gives things a unique fingerprint because that's what gets transcribed into proteins.

Well maybe a very successful treatment is the way to go rather than a cure then. With a topical libosomal delivery system containing this treatment, one designed to degrade instantaneously once absorbed into the blood stream, you could destroy follicle receptors daily. Don't know if this is any better than ASC-J9?

 

[Boba155]

Very true Rabid.

Another possibility which I like even more is deleting the gene that causes miniaturization of the hair follicle, i.e. the gene that the DNA Polymerase/AR complex transcribes that causes miniaturization of the follicle. Anyone know what gene this is?

We could easily silence this one, and the best part would be that it doesn't matter if it is systemic, since only one tissue expresses it.

 

[Rabid]

Aren't there way more than just one gene involved? male pattern baldness is a multi-factorial process!

 

[Bryan]

Another possibility which I like even more is deleting the gene that causes miniaturization of the hair follicle, i.e. the gene that the DNA Polymerase/AR complex transcribes that causes miniaturization of the follicle. Anyone know what gene this is?

We could easily silence this one, and the best part would be that it doesn't matter if it is systemic, since only one tissue expresses it.

There's no doubt whatsoever in my mind that there's vastly more than just a SINGLE gene which determines whether a hair follicle is stimulated by androgens (body hair) or suppressed by them (scalp hair). That has to do with the entire complex design and structure of the hair follicle, not just one single gene!

 

[Boba155]

Another possibility which I like even more is deleting the gene that causes miniaturization of the hair follicle, i.e. the gene that the DNA Polymerase/AR complex transcribes that causes miniaturization of the follicle. Anyone know what gene this is?

We could easily silence this one, and the best part would be that it doesn't matter if it is systemic, since only one tissue expresses it.

There's no doubt whatsoever in my mind that there's vastly more than just a SINGLE gene which determines whether a hair follicle is stimulated by androgens (body hair) or suppressed by them (scalp hair). That has to do with the entire complex design and structure of the hair follicle, not just one single gene!

So our only choice is the AR gene... which every tissue has...

f***.

Any suggestions for exclusive follicle delivery?

 

[Boba155]

Substantially

That means that some of the siRNA will enter into the bloodstream, and will then makes it's way to the testicles.

 

[Rabid]

Substantially

That means that some of the siRNA will enter into the bloodstream, and will then makes it's way to the testicles.

I think the more advanced liposomes can be designed to rapidly degrade once in the blood-stream.

 

[Rabid]

Never mind, looks like they can't.

 

[Boba155]

Although it does make one wonder, Rabid, how far would the remaining liposomes actually make it through the blood stream. The top of the head is quite a far distance from the testicles/prostate, do you think surrounding red blood cells would just uptake these as they moved down the bloodstream?

 

[freakout]

The gene is present in all 50 trillion cells in every organ; the brain, heart, kidney. What is the gene doing there?