Dual CRISPR therapy + long-acting antiretroviral drugs to clear HIV from the body
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Dual CRISPR therapy + long-acting antiretroviral drugs to clear HIV from the body.
AIDS (AIDS) is the abbreviation of Acquired Immunodeficiency Syndrome, which is caused by HIV infection .
HIV is a retrovirus that can attack the human immune system. It takes the most important CD4 T cells in the human immune system as its main attack target, and destroys the cells in large numbers.
After a incubation period of several years, even as long as 10 years or longer Later, it develops into an AIDS patient, causing the body to lose its immune function. Due to the extreme drop in resistance, various infections will occur.
In the later stage, malignant tumors often occur, and even the whole body fails and dies.
According to the World Health Organization (WHO) report, there are more than 38 million AIDS patients in the world.
Although antiretroviral therapy (ART) can control the progression of AIDS and even allow people living with AIDS to live like normal people, the therapy does not cure AIDS, it just suppresses the HIV virus in the body at a lower level.
Patients must adhere to daily medication throughout their lives. Once the medication is stopped, the HIV virus in the body can replicate rapidly, leading to the development of AIDS.
For the vast majority of AIDS patients, the biggest obstacle to a complete cure of AIDS is the virus reservoir in the body, that is, the HIV virus hidden in the cells. How to completely clear the virus reservoir in the body is the key to curing AIDS.
On May 1, 2023, researchers from Temple University and the University of Nebraska Medical Center published a paper in the Proceedings of the National Academy of Sciences (PNAS) entitled: CRISPR editing of CCR5 and HIV-1 facilitates viral Research paper on elimination in antiretroviral drug-suppressed virus-infected humanized mice .
The study showed that using CRISPR-Cas9 gene editing technology to knock out the CCR5 gene and target the LTR-Gag of the HIV-1 virus, combined with long-acting slow-release antiretroviral therapy (LASER ART) , can cure about 60% of patients. Complete clearance of HIV-1 virus in humanized mouse model.
In July 2019, the team published a paper in the journal Nature Communications [2] , which developed a long-acting slow-release antiretroviral therapy (LASER ART) , combining it with CRISPR-Cas9 gene editing technology, 29% The HIV virus in the humanized mouse model was completely cleared.
This is the first time HIV has been removed from the genome of a living animal, marking a key breakthrough in curing HIV infection.
A year later, the team advanced the research to non-human primates, and the results were published in the journal Nature Communications in November 2020 [3] .
Shortly after infection, the HIV virus integrates its own genome into the human genome, so current antiretroviral therapy (ART) alone can only suppress the HIV virus but not cure it.
The HIV virus remains in the patient’s body, so drugs must be taken every day for the rest of his life to suppress them, which can lead to drug resistance and other complications.
That’s why we need to develop a treatment that clears the HIV virus from the body, only in this way can we truly cure AIDS.
In this latest study, the research team developed a rigorous research protocol, first injecting a long-acting sustained-release antiretroviral drug (LASER ART) into a humanized mouse model infected with HIV .
A month later, the research team used CRISPR-Cas9 gene editing technology to knock out the CCR5 gene in these mice.
CCR5 is the receptor for HIV-1 virus infection and invasion of human cells, and the deletion of CCR5 gene will prevent HIV virus from further infecting and spreading between cells. According to previous research data, 7 days after gene editing, the expression level of CCR5 was minimized.
At this time, the research team performed a second CRISPR-Cas9 gene editing, targeting LTR-Gag, to clear HIV-1 DNA integrated in the genome, a step consistent with the team’s 2019 published study.
Next, the research team continued to observe these mice for 2 months.
The research team used a variety of highly sensitive detection techniques to ensure that no HIV copy was missed, including blood and all organs known to be infected by the HIV virus.
The results showed that the HIV virus in the body of 6 of the 10 mice in the treatment group was completely eliminated, and the results of the repeated experiment showed that the HIV virus in the body of 5 of the 9 treated mice was completely eliminated.
The research team said that the advantages of this treatment strategy are twofold. First, CRISPR gene editing is still the preferred method for permanently eliminating HIV virus.
Second, knocking out CCR5 through CRISPR gene editing can further promote the elimination of HIV virus.
As for why some mouse models still show HIV virus rebound after treatment, it is likely that the efficiency of the drug delivery system is not enough.
The effectiveness of this CRISPR + antiretroviral combination therapy is unquestionable, but a more efficient delivery system is needed .
It is worth mentioning that based on these results, the research team founded a company called Excision BioTherapeutics , which will be approved by the US FDA in 2021 to carry out clinical trials for AIDS treatment based on CRISPR gene editing.
The therapy is currently in Phase 1/2 clinical trials. In addition, since the adeno-associated viral vector (AAV) used in the study can only be administered once, the research team is also developing nanocarriers that can be administered repeatedly, as well as other viral vectors.
In addition to treating AIDS, Excision ‘s R&D pipeline also includes the use of CRISPR gene editing technology to eliminate hepatitis B virus (HBV) , herpes simplex virus (HSV) , papillary polyoma vacuolar virus (JCV) , etc.
Paper link :
1. https://www.pnas.org/doi/10.1073/pnas.2217887120
2. https://www.nature.com/articles/s41467-019-10366-y
3. https://www.nature.com/articles/s41467-020-19821-7
Dual CRISPR therapy + long-acting antiretroviral drugs to clear HIV from the body.
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