Macaques cured of immunodeficiency
Neuroscientists have removed an HIV-like virus from the primate genome
Olga Ivanova, Naked Science
The work of Mancuso et al. CRISPR based editing of SIV proviral DNA in ART treated non-human primates is published in the journal Nature Communications. SIV is a monkey immunodeficiency virus that causes persistent infections in at least 45 primate species (excluding humans). Scientists from the Lewis Katz School of Medicine at Temple University (USA) in 2019 for the first time removed HIV from the DNA of mice.
The same group of researchers conducted a new experiment, during which they successfully edited SIV in the genome of rhesus monkeys for the first time. The model of an animal infected with the SIV virus, according to experts, is an ideal model for the recurrence of HIV in humans.
To do this, the team has developed a gene editing construct that can reach infected cells and tissues that serve as reservoirs for SIV and HIV. In these cells, the virus is integrated into the host DNA. Due to such reliable "storage", diseases caused by such viruses are so difficult to cure. Antiretroviral therapy is aimed at removing pathogens from the blood, but as soon as it stops, viruses "come out" of "shelters" and resume their activities again.
The work began with the development of a design for editing CRISP-Cas9 genes specific to SIV. Then, the cell culture confirmed the effectiveness of the design, which cleaved the integrated DNA of the virus from the DNA of the host cell in the right place, without fear of "hitting" neighboring genes. Next, the scientists packed this construct into a carrier of the adenoassociated virus – AAV9 (it is assumed that it does not cause disease in humans), so that it could be injected into the vein of infected SIV macaques.
At the same time, the researchers selected three infected macaques, and the other three – healthy ones – were a control group. AAV9-CRISPR-Cas9 was administered first, and blood and tissue samples were taken from all subjects three weeks later. As a result, it was shown that the gradual excision of SIV DNA from tissues and blood cells occurred with high efficiency. Scientists hope to transfer the data of their work to clinical studies in humans.
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