Going to cure AIDS further! Antiviral therapy eliminates HIV in animals
"Nature-Communication" recently launched a heavy paper in the field of AIDS research. Scientists have developed a combination therapy that combines the delivery system of antiretrovirals with the CRISPR-Cas9 gene editing technology. According to an official press release, this therapy removes HIV-1 DNA from the genome of living animals for the first time.
Researchers commented that the study "marks a crucial step in the development of new therapies to cure human HIV infection."
According to UNAIDS estimates, more than 5,000 people are infected with HIV-1 every day in the world. At present, infected people mainly rely on various antiviral drugs for treatment. Antiretroviral therapy (ART) can effectively reduce the viral load in patients and reduce the risk of viral infection.
With the unremitting efforts of scientists, existing therapies have turned the once terminally ill disease into a controllable chronic disease, and scientists are still moving toward the goal of curing AIDS.
ART therapy requires the infected person to take the drug for life, because this therapy can inhibit the replication of the HIV virus, but it cannot eliminate the virus from the body. If you stop the drug, the HIV virus in the body will come back, re-copy and promote disease development.
The reason why HIV has the ability to "rebound" is because when the virus attacks the body's immune system, it integrates the DNA sequence into the genome of the cell and hides it in the human body.
To truly eliminate the "cure" effect of HIV, DNA fragments integrated with the virus are removed from infected cells and tissues.
Professor Howard Gendelman of the University of Nebraska Medical Center and Professor Kamel Khalili of the Lewis Katz School of Medicine at Temple University and colleagues developed a The combination therapy aimed at eliminating HIV virus consists of a new method of ART delivery and CRISPR gene editing technology.
â–² Two correspondents of the study, Professor Howard Gendelman (left) and Professor Kamel Khalili (right) (Source: Research Institute official website)
Specifically, Professor Gendelman and his collaborators have developed a long-acting, slow-release ART therapy in which modified antiviral molecules are packaged in nanoparticles that carry the drug into the hiding place of HIV. This mode of administration can slowly release the drug within a few weeks, achieving the purpose of inhibiting viral activity for a long period of time.
Professor Khalili's team used the technology developed by CRISPR-Cas9 to "cut" HIV DNA fragments in infected cells. While long-acting sustained-release ART therapy inhibits HIV replication at a lower level, CRISPR-Cas9 begins to work.
The research team verified the feasibility and effectiveness of this combination therapy through animal experiments. They first created a humanized mouse model of HIV infection. Then, two independent experiments were performed, and a total of 13 confirmed infected mice were administered combination therapy.
â–² Schematic diagram of infection and administration therapy (Source: Reference [1])
After continuous treatment, blood, lymphoid tissue, bone marrow and brain tissue were examined by a number of techniques within 5 weeks of treatment. The results showed that nearly one-third of the mice receiving the combination therapy did not detect the HIV virus, and it can be considered that the HIV virus DNA in the mouse cells and tissues was completely eliminated.
In contrast, HIV is easily detected in mice that receive one of these treatments alone. In addition, the test results also showed that CRISPR-Cas9 off-target was not detected.
The positive results of the mouse experiment show the prospect of this combination therapy to cure AIDS. According to the news released by Professor Khalili in the research institute, they plan to carry out further research to promote the experiment of non-human primates within one year, and It is possible to conduct clinical trials in human patients.
Reference material
[1] Prasanta Dash et al., (2019) Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nature Communications. DOI: 10.1038/s41467-019-10366-y
Source: Academic Jingwei
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