25 August 2020

Herpes gene therapy

New gene therapy cleansed 90% of herpes traces from infected cells

However, it will be possible to use it in practice only in a few years

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American molecular biologists have developed and tested experimental gene therapy on mice, which "cuts out" more than 90% of the fragments of the herpes virus genome from infected human cells. This should prevent signs of infection from reappearing on the lips and other parts of the body, the scientists write in an article for the scientific journal Nature Communications (Aubert et al., Gene editing and elimination of latent herpes simplex virus in vivo).

"For the first time, we have destroyed most of the traces of the herpes virus in the body of an experimental animal. I hope that our results will make colleagues think that scientists can not only contain this virus, but also actively fight it," said one of the authors of the study, professor at the Fred Hutchinson Cancer Research Center (USA) Kit Jerome.

The herpes virus is the causative agent of one of the most common human infections. There are several different types of this virus that affect different parts of the body. For example, the HHV1 virus causes a cold on the lips, HHV2 penetrates into the genitals, and HHV6 and HHV7 cause pseudocrush – a short fever and rash.

For quite a long time, herpes, especially HHV1, was considered a fairly harmless virus. However, scientists have recently discovered that it can provoke the development of Alzheimer's disease, multiple sclerosis, encephalitis, genital cancer and other diseases. A person remains a carrier of this virus for the rest of his life, since there are no vaccines against it yet.

Molecular "scissors" for herpes

Jerome and his colleagues have taken the first step towards solving this problem. They have created an experimental gene therapy that can "cut out" traces of the virus from the genome of infected cells. To do this, scientists used two different DNA editing systems based on the so-called meganucleases.

This is what scientists call special enzymes of bacteria and archaea that can find specific sequences of genetic "letters"-nucleotides in the DNA chain and cut them out. Meganucleases work more accurately than other genomic editors, since they read sections of several dozen "letters" long.

The main disadvantage of meganucleases was that they are configured to work with one specific sequence of nucleotides. And changing it, as the practice of the last three decades shows, is incredibly difficult. To create two similar enzymes that can recognize key parts of the genome of the HHV1 virus and cut them from the DNA of humans or other mammals, Professor Jerome and his colleagues spent several years.

After testing the work of these enzymes on cell cultures, scientists tried to cure mice from herpes. To do this, the researchers packed "instructions" for assembling meganucleases inside an adenovirus that could not embed its genome into the DNA of humans or animals. As a result, the enzymes successfully coped with their task, destroying 92% of the viral DNA in infected neurons and other rodent cells.

Observing the state of health of mice over the next month, scientists did not record hints that the herpes virus had "resurrected" and began to infect cells again. This suggests that such gene therapy should protect a person from the return of infection.

The researchers believe that in practice this therapy will be able to be used no earlier than in a few years, when all clinical trials and safety tests are over. In parallel, Professor Jerome and his colleagues plan to develop a similar gene therapy to combat the sexual variety of herpes. Scientists assume that it will take them at least three years.

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