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Weapon against HIV at fingertips

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09.05.2017

The efficient treatment of HIV infection has been impossible until now, due to the capability of the virus for hiding away. However, the researchers of the University of Pittsburgh have found a new method to manage this incurable disease ? namely, blocking its replication through the removal of HIV DNA from the genomes of living animals. This leads to putting both the replication of HIV-1 and occurrence of further infections to a halt, along with the removal of viruses themselves. The treatment included a recombinant viral vector meant to replace a mutated DNA fragment of a given cell ? being responsible for the replication of virus ? after having been introduced to one's organism. The technology, operating on the basis of enzymes and the "find-and-replace" principle, was dubbed "CRISPR/Cas9". The research was carried out by a number of individuals, including Kamel Khalili, PhD (the inventor of CRISPR/Cas9 viral cell modification method) and Wenhui Hu, PhD (a specialist in the field of molecular neuroscience, particularly ? gene regulation, signal transduction and gene therapy). The first research of this kind reaches back to 2016 when transgenic rats and mice subject to it had DNA HIV-1 incorporated into the genome of their tissues. This is when it became possible to remove the virus from approximately 60% of infected body areas in animals, while this year's research has proven even more effective. Three animal models were used this time. "Our new research is more complex", says Mr. Hu, PhD. "We have confirmed the effectiveness of our previous works, as well as we have improved it. Moreover, we have confirmed the effectiveness of the treatment strategy of this kind both in the case of acute and hidden infection" ? he adds.

In the course of testing, the first group of mice was infected with HIV-1, while the other one ? with an acutely-affecting version of EcoHIV (a mouse equivalent of the human virus). Successively, the third group was constituted by mice "humanised" with the use of human immune cells that had been infected with HIV-1.

In the case of group one, it has become possible to deactivate HIV-1 with the use of CRISPR/Cas9 method, as well as to reduce the genetic expression to 95%. The second group posed a certain challenge to the researchers, as the virus both replicates and spreads rapidly over the whole organism affected during acute infection. "Thanks to the mice infected with EcoHiv, we could precisely investigate the capability of CRISPR/Cas9-based strategy for efficiently blocking the replication and preventing systemic infection", stressed Khalili, PhD. The efficiency of this therapy reached 96% which means that the method also works in the case of acute courses of infection. The third group, composed of "humanised" mice, reflected the case of hidden infection. The virus had been concealed in the area of the genome of human T cells, due to which the detection of virus-affected fragments of genetic material was hindered. In spite of the fact, it became possible to excise fragments of this virus from all tissues subject, and so as early as during the first approach to treat the infection with CRISPR/Cas9 method applied. The success of this research is of extreme importance as a step along a hard way of treating HIV sufferers. The successive stage is to repeat the tests with primates involved, e.g. in order to demonstrate the elimination of DNA HIV-1 from nerve cells inside a brain. The final goal relies on conducting research involving infected humans and the commercialisation of this treatment method.

Source: Molecular Therapy, Volume 25, Issue 5, 03.05.2017, pp. 1168-1186.

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