Brian Hanley's garage gene therapy

[Mega [Andreas Stuermer]]

Hey guys. I came across this story
 https://www.technologyreview.com/s/603217/one-mans-quest-to-hack-his-own-genes/?utm_campaign=internal&utm_medium=homepage&utm_source=cover-story

It seems that somebody injected himself with plasmid DNA and electroporated it then. His goal was to express human growth hormone,  to increase his muscle mass (body size will not affected after age 25 obviously).

Besides any ethical concerns, I wonder if this is *safe*. For what I know, the treatment may cause anti-dsDNA antibodies and anti-nuclear antibodies, no?  the worst outcome would then be autoimmune disease such as lupus?
On the other hand some studies suggest that  injecting DNA doesn't necessarily produce these antibodies, this happens mainly if proteins are bound to the therapeutic DNA.

But the DNA will be amplified by bacteria so it will be methylated (e.g. Dam methylation) - wont that cause immune response and/or silencing?

[ukitel]

He might have used a methylation deficient strain to bypass that problem
I don't think the mere presence of DNA around is gonna cause the production of anti-dsDNA antibodies. I had a quick look and it seems indeed that repeated injection of DNA in healthy mice does not cause the formation of anti-dsDNA antibodies. However, mice prone to autoimmune disease do, after repeated injections.
http://www.nature.com/gt/journal/v8/n17/full/3301537a.html

Also, some viral infections cause production of anti-dsDNA antibodies, but this is transient.

All together, even if it cannot be excluded, I think that such development of an autoimmune disease following DNA injection is quite unlikely.
It is more probable that he would, on the other hand, develop anti-GH antibodies (if he gets GH expression at all).

[Mega [Andreas Stuermer]]

Alright, sounds about right. 
But weighting the risks against the benefits - I think if there's a chance to develop lupus, that's not worth 30% more muscle mass... It is DNA after all, coming in contact with your body so there probably is no way to entirely rule that out right? 

[Raza]

Aside from the safety of the process, I wouldn't want to overexpress growth hormone. That's lifespan-reducing stuff in animals, and there's at least circumstantial evidence for it applying in humans (correlational research showing that people who sleep less live longer, despite all the stress-related drawbacks).

[Bryan Bishop]

On Thu, Jan 12, 2017 at 3:53 PM, Mega [Andreas Stuermer] <masters...@gmail.com> wrote:

Hey guys. I came across this story

Here is some discussion on the topic (starting around 18:31):
http://gnusha.org/logs/2017-01-12.log

- Bryan
http://heybryan.org/
1 512 203 0507

[ukitel]

I guess the risk/benefit analysis is in the end personal.
Anyway, imho, the chance of developing some autoimmune disease is connected to repeated injections rather than an occasional one.
There actually might be a way to bypass this risk, by inducing a transient immunesuppression, e.g. a short cortisone treatment before the DNA injection, but this is only speculation from my side.