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How Far Is It to Cure AIDS?

AIDS is the acquired immunodeficiency syndrome caused by the human immunodeficiency virus (HIV). Since first reported in 1981, AIDS has caused nearly 33 million deaths. AIDS is mainly spread through blood and body fluids, such as unclean sex, mother-to-child transmission, and injection of drugs and unclean blood products. As HIV attacks the human body’s CD4+ T cells, it can cause patients to gradually lose immune function, who generally die from various secondary infections or malignant tumors.

 

As a retrovirus, HIV can integrate its genome into the chromosome of the host cell, which means that it is impossible to completely cure AIDS patients by relying on antiretroviral therapy (ART), which forces scientists to explore effective methods to eliminate chronic HIV infection and cure AIDS.

 

December 1 of each year is the “AIDS Day” established by the World Health Organization, aimed at calling on people to raise awareness of AIDS, to care for AIDS patients, and to prevent the spread of AIDS.

 

On November 27, 2020, researchers from Temple University and University of Nebraska Medical Center published a research paper titled: CRISPR based editing of SIV proviral DNA in ART treated non-human primates in Nature Communications. The study successfully edited and eliminated the SIV-a virus that is closely related to HIV in the genomes of non-human primates, which is a crucial breakthrough in AIDS research, which also makes mankind closer than ever to develop a complete cure for AIDS.

 

Simian immunodeficiency virus (SIV) is a retrovirus that can affect at least 33 African primates. In non-human primates, SIV behaves very similarly to HIV. Therefore, the rhesus monkey model infected by SIV is the most ideal large animal model for simulating human AIDS patients infected with HIV.

 

As an emerging technology, CRISPR is widely used in the fields of gene editing, gene therapy, nucleic acid localization, and nucleic acid detection. On October 7 this year, the 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer A Doudna, in recognition of their outstanding contributions in the field of CRISPR gene editing.

 

Scientists pointed out that CRISPR technology can be applied to treat AIDS to completely eliminate the HIV integrated into the chromosomes of host cells.

 

The researchers first designed a SIV-specific CRISPR-Cas9 gene editing tool. Subsequently, the CRISPR-Cas9 gene editing component was packaged into an adeno-associated virus type 9 (AAV9) vector. Among the three randomly selected rhesus monkeys, two received an AAV9-CRISPR-Cas9 injection, and the other served as a control. Three weeks later, the researchers collected blood and tissues from these rhesus monkeys. Sample analysis showed that in rhesus monkeys treated with AAV9-CRISPR-Cas9, the CRISPR-Cas9 gene editing system that specifically targets SIV was widely distributed to tissues such as bone marrow, lymph nodes, and spleen, and has reached CD4+ T cells—an important host cell for HIV. Through genetic analysis, it was found that in two rhesus monkeys injected with AAV9-CRISPR-Cas9 intravenously the SIV integrated genome in the infected cells was effectively eliminated. The removal efficiency of lymph nodes is relatively high. The research team also conducted similar experiments in other animal models, and confirmed that the AAV9-CRISPR-Cas9 system can effectively remove HIV-1 integrated DNA from cells and tissues of humanized mouse models infected with HIV-1.

 

The huge research progress is expected to completely end the nightmare of AIDS in humans, which can not be separated from the non-human primate disease models. Non-human primates share many similar biological characteristics to humans. Rhesus monkey has 75%-98.5% homology with human in genetic material, which is an ideal animal model for human diseases and basic research, such as infectious diseases, genetic diseases, cardiovascular diseases, behavior, neurobiology, reproductive physiology, pharmacology and toxicology, and oncology.

 

 

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