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:
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.
- Take an Adenoassociated Virus (AAV) that has already been extensively characterized and utilized in other studies.
- Put in the genetic information that codes for an antibody that you know binds tightly to nicotine.
- 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.