T-lymphocytes will learn to protect themselves from HIV

Scientists artificially accelerated human evolution to fight HIV

RIA Novosti (ask them what evolution has to do with it in general and man in particular – VM).

The CRISPR/Cas9 genomic editor helped biologists artificially "force" the evolution of the human immune system, which scientists hope will help in the near future to create a universal cure for HIV based on antibodies created in this way, according to an article published in the journal Cell Reports (Hultquist et al., A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells).

"This is what virologists dealing with HIV have long wanted to get. I hope that our development will make this task, which seemed impossible a year ago, something that we can all implement in the near future," says Judd Hultquist from the University of California at San Francisco (in a press release, Researchers Use CRISPR to Accelerate Search for HIV Cure – VM).

The CRISPR/Cas9 genomic editor, called the main scientific breakthrough of 2015, was created by American scientist Feng Zhang and a number of other molecular biologists about three years ago. Since then, it has undergone several upgrades that allow scientists to use it to edit the genome with one hundred percent accuracy.

It can be said that the fight against HIV is a kind of "return to the roots" for CRISPR/Cas9 – it originally developed inside bacteria hundreds of millions of years ago precisely to protect against retroviruses, and only in 2012 Feng Zhang and his colleagues adapted it for editing the genome of multicellular creatures.

Today, many scientists are trying to use this genomic editor in order to "cut" the genetic code of HIV from the DNA of infected cells and thereby clear them of infection. The "pure" implementation of this task, as Hultqvist and his colleagues note, is extremely difficult, so the authors of the article decided to approach it from a different angle – to force human immune cells to independently develop protection against the immunodeficiency virus.

To do this, scientists had to create a special technique for introducing the Cas9 protein and RNA templates, according to which it performs editing, into immune cells, since infection with a special retrovirus, traditional for such manipulations, for obvious reasons does not work. It turned out that such an "injection" can be carried out by expanding the pores in the cells with the help of an electric current, through which Cas9 and RNA molecules will freely penetrate inside.

Figure from an article in Cell Reports – VM

Having solved this problem, Hultqvist and his colleagues created a special version of CRISPR/Cas9, which allowed them to automatically introduce mutations into the CXCR4 and CCR5 genes and 43 more DNA sites that HIV uses to penetrate T cells, and tested several hundred "mutant" variants of these genome regions.

This approach allowed biologists to identify several of the most important genes – LEDGF and TNPO3, disabling or changing which increase the resistance of immune cells to HIV, and "grope" several possible ways to create a universal gene vaccine against this disease. In addition, the authors of the article hope that their "forced evolution" approach will help develop conventional drugs that more effectively suppress the reproduction of the virus and do not cause side effects, like modern antiretroviral drugs.

In the near future, the authors of the article plan to improve this approach by introducing not only random mutations in the DNA of immune cells, but also copying those parts of DNA that are contained in T-cells of people who are immune to HIV for natural reasons. Similarly, according to Hultqvist, it is possible to develop drugs for other incurable diseases.

Portal "Eternal youth" http://vechnayamolodost.ru  31.10.2016