GMO Virus for Nicotine Addiction

I used to think gene therapy was an absurd 'solution' for HIV/AIDS.  Well, 'absurd' is putting it lightly.  I thought gene therapy was a perverted solution-- Even if it 'worked', it would only be available for the richest people in the richest countries, not the millions and millions and millions of individuals living in poverty who need a solution the most (not just the poor abroad, I doubted the poor right here in the USA could get this kind of therapy).

But in the six years Ive been writing at ERV, my stance on gene therapy has changed from 'Thats disgusting, and Im actually kind of angry anyone would suggest that' to 'This might actually work.'

Papers like this are why.  In a very short amount of time, we are getting better and better at gene therapy.  Absurdity is inching towards reality:

AAV-Directed Persistent Expression of a Gene Encoding Anti-Nicotine Antibody for Smoking Cessation

For one reason or another, some people use tobacco products (cigarettes, cigars, pipes, chew, whatever).  This leads to 440,000 premature deaths every year in the US (not to mention all the people living with forms of cancer, COPD, etc). So, lots of people try to quit smoking.  Even with patches/gum/drugs/therapy, the vast majority, 70-80%, quit quitting within 6 months.

Well, what if a genetically modified virus could make you quit by taking away the power of nicotine?

A GMO virus that would make it so no matter how much you smoked, you could not feel the effects of the nicotine.  You could inject yourself with nicotine, and nothing would happen. No reason to smoke anymore.  This GMO virus would essentially *make* you quit smoking.  It would *make* you get through withdraw, because you would have no other options.  No way of getting a hit. Once you were injected with this virus, there would be *no* going back.

How would such a virus work?

Theoretically, an anti-nicotine vaccine could be used to get peoples immune systems to make anti-nicotine antibodies.  These antibodies would stick to the drug, and prevent it from getting into the brain before it got degraded. But with a vaccine, you have to deal with problems like what to put in the vaccine as a target, what to put in as an adjuvent, what kind of dose you need, how many boosters you need, whether people actually make antibodies that can neutralize the drug, how long those antibodies stick around, and so on.

You could circumvent a lot of trouble if you just inject people with the 'right' antibody to nicotine-- Its called passive immunotherapy.  But that gets expensive, and it doesnt last for very long.

But with a GMO virus, things get curiously easier.

  1. Take an Adenoassociated Virus (AAV) that has already been extensively characterized and utilized in other studies.
  2. Put in the genetic information that codes for an antibody that you know binds tightly to nicotine.
  3. Figure out the smallest dose necessary to get the desired response, and shoot em in!

AAV are not retroviruses, but they do insert their genomes permanently into the cells they infect.  With this approach, you are basically telling the immune system what the 'right' answer to nicotine is, and they happily go about making that 'right' answer, whether nicotine is around or not, endogenously.  So maybe think of this approach as like permanent passive immunotherapy.

This might sound neat on paper, but does it work in real life?

So far, yes! ... In mice!

The more AAV-Anti-Nicotine-Antibody you infect the mice with, the more antibodies you can find in the mouse bloodstream.  And, the antibodies that are there last at least 18 weeks, which isnt too bad considering there was only one dose of virus, and mice only live a year or two.

And, the antibodies worked.  When the mice were injected with nicotine, the antibodies were capable of keeping nicotine in the blood serum, and out of the brain (if it doesnt get in the brain, you dont get the physiological effects).  The control mice had a decrease in blood pressure and heart rate, as well as a decrease in locomotion, while absolutely nothing happened in the treated mice (huh, I thought all that would go up after nicotine, but I guess thats part of the 'mellowing' effect smokers like).

Like I said, these vectors are already pretty well characterized, and are already in clinical trials for some diseases.  Im guessing that it wont be too hard to get this therapy in the human trial pipeline.

Huh.  Gene therapy for nicotine addiction.

Maybe gene therapy for HIV/AIDS isnt such an absurd idea.

More like this

How likely is it that a gene inserted in this manner gets passed on to offspring? If that can happen, I'm not really sure whether to consider that a positive or negative side effect.

I like this, it sounds so neat and clean a solution! I'm sure it won't be as easy as it sounds, but if it were...

Hayden: Good news (for having people not panic, anyhow). In order to pass this on to your offspring, it would have to infect germ line cells (sperm/eggs); as long as the AAV can't infect those cells (and I believe at least some of the strains out there don't) then we're good to go. As well, if you're using some of the most gutted AAVs, then as cells divide they get lost anyway. Imagine that (worst case scenario) the mom's egg cell somehow has two copies of the AAV at fertilization. Because the AAV can't replicate/copy itself, by the time you reach fetus size (or anywhere in between), there are still only two copies of the AAV in the entire organism - that is, only one or two cells still have it, if neither of those cells has died, and if the AAV genome hasn't gotten "cleaned up" (destroyed as garbage) during development. It is kind of a tough call whether we would be better off if we could pass this sort of thing on down the line to our children ;) But for now I think I'm good with being safe, rather than potentially sorry.

Let’s hope. I’ve quit tobacco; but I still have a nicotine addiction that I satisfy with one of those “electronic cigarettes”. That’ll be the next thing I work on.

Heavy smoker here.

I usually smoke around 30 cigarets a day, more or less. When I get in my "low health" period, I can spend a week or more without smoking a single one, I'm too concentrated on dealing with the pain from my illness. And there are no ill effects related to this break in nicotine intakes, at least for me.

What I'm trying to say is that nicotine is a very tiny portion of what makes a smoker addicted. The smell, the taste, the gesture, these are all part of the smoking experience. Eliminating one of the causes of dependency is a pretty good idea, but it would need to be accompanied by a strong psy follow up.

Because, let's face it, even if a smoker doesn't feel the effects of nicotine anymore, they will still have the habit of smoking. I've tried substitutes (eucalyptus cigarets bought in pharmacy) and they worked great, as in I didn't need the nicotine, because there was none in those. The taste, though, was awful. But the gesture, smell... were kinda there.

So, GMO to block nicotine addiction? Yes! But more might need to be made to have a heavy smoker quit altogether.

By Phil Giordana FCD (not verified) on 10 Jul 2012 #permalink

Ouch, Phil - even at my worst I only went about a pack a day (granted, one day after a marathon work session I realized I was on my fourth pack, but that was the only time). I quit with the patch - even went one week short - and haven't looked back, not even with a room full of smokers. No desire. Maybe I'm unusual, I don't know. To break the habit I actually kept a cigarette with me for breaks, and when I went out with the rest for a smoke break, I just used the unlit cigarette like a real one - in my hand or on my lips. Never lit it and I even broke that habit after a while. Smoked 10-odd years, and been smoke free for...9, I think.

I'm curious to know what effect, if any, this might have on second hand smoke, or if this will prevent people from starting?

Phil, give e-cigs a try. I won't advertise here, but shoot me a message on the Facebooks and I'll give you my recommendation. Found one that feels like smoking, tastes better (although still tobacco-like), and has different strength cartomizers so you can wean yourself down to zero nicotine with no loss of flavor or mouthfeel. I quit for five years, started smoking again when Max died two years ago, and switched to e-cigs two months ago, and I'm already down to the half-strength cartomizers. And I've already got all my sense of taste and smell back.

By Optimus Primate (not verified) on 10 Jul 2012 #permalink

In reply to Phil at 4:49 pm:

"What I’m trying to say is that nicotine is a very tiny portion of what makes a smoker addicted."

I don't think that's right Phil. Yes, the side issues of smoking, the various rituals, play a very powerful role in the process (I smoked for most of my life, from the age of 11 until my early forties, so like you, I do know whereof I speakethish).

However, when I was at College in the 90s, in one of the psychology courses I took we studied nicotine addiction. I was informed through that course that nicotine is one of the most addicitve drugs known because unlike any other drug known at that time, as I recall, nicotine actually screws around with two, rather than the normal single, receptor sights (uptake sights? I hope I've remembered the correct terminology). So, when you try to quit, you are, in a sense, trying to quit two highly addictive drugs at the same time.

Now, I am in no way whatsoever a scientist, so if the many science-wise folks here can correct me on any of that that, please go right ahead and do so.

By John Greg (not verified) on 10 Jul 2012 #permalink

John: I'm not diminishing the addictive power of nicotine, I'm just saying it's only a part of cigaret addiction, at least for me.

I feel my addiction is more psychologic than physiologic because, as I said, I feel no ill effects when abruptly stopping my smoking for a week or more. Of note, I have a very low addiction resistance threshold. I smoke and I drink (I don't do any drugs, though).

My drinking habits clearly categorize me as an alcoolic, but I can also go weeks at end without a single drop of spirit, and I never experience DT, the shakes or any other averse effect. This might be the reason why I feel my addictions are more psychologic than physiologic.

I have before stopped drinking and smoking for periods up to 6 months in a row (ex girlfriend didn't like the habit) without withdrawal symptoms. Just a "want" feeling that was not hard to overcome.

I'm 34, and I've been smoking and drinking since I was 15. Ironically, I started those habits in...Florida :D And to be honest, I don't feel like quiting right now, because these are pleasures I really enjoy, either while composing, reading, interacting on blogs/forums or watching movies. I guess I'll stop altogether if it ever starts taking a toll on my health. But my current health problems are not related to smoking or drinking...

All that being said, if GMO can fight nicotine addiction, I'm sure it will help a lot of people.

By Phil Giordana FCD (not verified) on 10 Jul 2012 #permalink

"Swine flu vaccine linked to nerve disorder" is big news here in Canuckstan I'd really appreciate knowing what happened here.
Guillain-Barre Syndrome reported in 42 Quebec recipients.

"A GMO virus that would make it so no matter how much you smoked, you could not feel the effects of the nicotine. You could inject yourself with nicotine, and nothing would happen. No reason to smoke anymore. This GMO virus would essentially *make* you quit smoking. It would *make* you get through withdraw, because you would have no other options. No way of getting a hit. Once you were injected with this virus, there would be *no* going back."

It would not make you quit, if you have smoked say strong roll ups and move over to weaker you just smoke more to compensate. If this is logically translated to this scenario the person will go fxxxing bonkers trying to catch up and fail.

I think the suicide rate would esculate really.

bit like the nut who thought up vaccinations against all the illicit drugs, big problem, most of the best analgesics are based on them so that means you would never be able to take them, bad news for pain relief.

This tobacco vaccine has been thought up by non smokers and like a god solution it can't succeed. What does work is not smoking - banning inside is good and helpful, Alan Carr's books have good reviews from people who have tried it, you only need to not smoke the next one!

The instructor at at a U.S. Navy fighter flight school asked an incoming class how many of the students smoked. About half the hands went up.

He said, "Don't worry, before the end of this course you'll all be smoking."

Because it's a neurotransmitter analog, nicotine is both a highly effective drug (for treating nicotine addiction, or various vaguely defined disorders of mood and appetite) and an extremely toxic nerve poison. It's easy to get a rapidly lethal dose through the mouth, skin, or bloodstream.

Inhalation is actually the safest way to take it, which is why smoking is still popular and e-cigs are expensive. The amount absorbed per drag is small and very rapidly absorbed, so there's immediate feedback control on the timing and size of the next incremental dose. It's almost impossible to overdose by smoking.

So I worry about treatments that reduce the 'satisfaction' per dose, because the feedback system may lead to much higher quantities being absorbed. If the vaccine keeps it out of the brain, the damage to the rest of the body may be so much the worse.

Besides - Clockwork Orange!III

By John Scanlon, FCD (not verified) on 12 Jul 2012 #permalink

The only reason there is a nicotine receptor in the brain is because there is something in the brain that activates it. What is the cross-reactivity between this antibody and that endogenous substrate for the nicotine receptor?

By daedalus2u (not verified) on 12 Jul 2012 #permalink

Cool. Now, if only scientists can discover the cause of rampant gullibility, and discover a cure for that affliction.

We could eliminate most sorts of supernatural-quackery in a generation or two.....

By Bob Powers (not verified) on 12 Jul 2012 #permalink