According to a new study published online in Nature Communications, American scientists have successfully edited the SIV (simian immunodeficiency virus) from the genome of non-human primates, which is closely related to the human immunodeficiency virus HIV, or AIDS. Cause of disease). This breakthrough is an important step in HIV research and will bring researchers closer than ever to developing a treatment for human HIV infection.
A researcher from Temple University School of Medicine, who led the research, said: "We have demonstrated for the first time that a single inoculation of the CRISPR gene editing construct carried by the adeno-associated virus can edit the SIV genome from the infected cells of rhesus monkeys." This new work shows that the gene editing construct developed by the research team can reach infected cells and tissues. These tissues are called SIV and HIV virus reservoirs, which are cells and tissues where the virus is integrated into the host DNA and hidden for many years , Is the main obstacle to cure infection. The SIV or HIV in these virus banks is beyond the scope of antiretroviral therapy, which can inhibit virus replication and remove the virus from the blood. Once the antiretroviral therapy is stopped, the virus will emerge from its reservoir and replicate again.
In non-human primates, SIV behaves very similarly to HIV. The Rhesus monkey model of SIV infection studied in the laboratory is an ideal large animal model that can generalize human HIV infection.
In this new study, the researchers designed a SIV-specific CRISPR-Cas9 gene editing construct. Cell culture experiments confirmed that the editing tool can cut the integrated SIV DNA from the correct position of the host cell DNA. They then loaded the construct into an adeno-associated virus 9 (AAV9) vector, which can be injected intravenously into animals infected with SIV.
Researchers randomly selected 3 SIV-infected rhesus monkeys, each received an AAV9-CRISPR-Cas9 injection, and another rhesus monkey was selected as a control. Three weeks later, the researchers collected blood and tissues from the macaques. Analysis showed that in rhesus monkeys treated with AAV9-CRISPR-Cas9, gene editing constructs have been distributed in a wide range of tissues, including bone marrow, lymph nodes, and spleen, and reached a very important virus pool, CD4+ T cells.
In addition, researchers from Temple University conducted genetic analysis on the treated animal tissues and proved that the SIV genome can be effectively lysed from infected cells. The efficiency of lysis varies from tissue to tissue, but it clearly reaches a high level in the lymph nodes. The researchers said that this is an important progress in the process of ending HIV. The next step is to evaluate this treatment over a longer period of time to determine whether it can completely eliminate the virus and even free the subjects from antiretroviral therapy.