Organophosphate vaccination

"Genetic inoculation" protected mice from chemical weapons

Sergey Vasiliev, Naked Science

American biologists have introduced a gene into the DNA of mice that gave them complete protection from organophosphorus nerve agents, including sarin and agent VX.

Despite all the prohibitions and promises, chemical warfare agents pop up every now and then in modern conflicts around the world. In case of a lesion, an antidote should be administered as soon as possible to neutralize the effect of the toxin. But American scientists have tested a new approach that allows you to produce medicine directly in the body.

The practical application of such a "combat vaccine" in humans is still far away. However, in an article published in the journal Science Translational Medicine (Betapudi et al., Gene therapy delivering a paraoxonase 1 variant offers long-term prophylactic protection against nerve agents in mice), Nageswararao Chilukuri and his colleagues from the Medical Research Institute of Chemical Defense of the U.S. Army report the first successful experiments with laboratory mice.

We are talking about protection against organophosphate compounds that are used as nerve agents, such as sarin, tabun, VX or Novichok. The target of such toxins is the acetylcholine mechanism of signal transmission between nerve and muscle cells. Disruption of its work causes spasms, paralysis, and in the worst case — death from respiratory arrest.

Atropine and other organophosphate antidotes prevent their binding to acetylcholine receptors and give the body time to neutralize and eliminate the toxin molecules. It is easy to understand that the antidote should be taken as soon as possible after the toxic substance enters the body, but even in this case, certain damage to the nervous system will be inflicted.

Therefore, American scientists decided to go the other way. They drew attention to the enzyme paraoxonase 1 (Paraoxonase 1, PON1), which is involved in the neutralization of organophosphates. Some time ago, this protein was artificially "modified" to increase efficiency and even tested on animal models. Unfortunately, this approach is impractical: the body's immune system rapidly attacks the enzyme that has entered the blood and itself incapacitates it.

To get around this problem, this time they used not the protein itself, but its gene, which was introduced into the liver cells of laboratory mice with the help of a viral vector. And indeed, soon significant amounts of "modified", recombinant PON1-IF11 were found in the blood of animals. The protein level remained stable for at least five months, making the rodents virtually insensitive to the effects of the poison. For a month and a half, the mice survived nine injections of lethal doses of organophosphates, including the same sarin and tabun.

And although the practical application of such a "vaccine" is still far away, Chilukuri and his co-authors note that it will be useful not only on the battlefield. Organophosphate poisoning is more often encountered by ordinary farmers: these compounds are widely used as insecticides. They are not nearly as powerful and dangerous as chemical warfare agents, but they can accumulate and cause no less dangerous poisoning. Therefore, "organophosphate vaccination" may be necessary and important in a completely peaceful life.

Portal "Eternal youth" http://vechnayamolodost.ru