2023-05-19 14:04:28
A combined approach that aims to eliminate HIV using two types of CRISPR gene editing has succeeded in eliminating the virus that causes AIDS, according to a report published in “Proceedings of the National Academy of Sciences». One CRISPR molecular scissors removes genes for the CCR5 receptor, which HIV uses to enter T cells, while another removes HIV genes from cells that are already infected. So far, this approach has only been tested in mice, but the research could set the stage for human cure studies.
“The idea of linking the cleavage of HIV-1 DNA with the inactivation of CCR5 using gene-editing technology is based on observations of reported cures in human patients with HIV,” says Kamel Khalili, of the Temple University Center for Neurovirology and Gene Editing, in a university news release. The new research is the first to use these unique combinatorial therapies to cure viral infection from HIV-infected humanized live mice. .
«We combine the successes of gene therapies and antiretroviral drugs created at UNMC and Temple, respectively», says researcher Howard Gendelman.
“HIV-1 DNA cleavage and CCR5 inactivation were linked by gene-editing technologies based on observations of reported cures in human HIV patients,” he says. Camel Khalili. “In the few cases of human HIV cures, patients underwent bone marrow transplantation for leukemia, and the donor cells that were used carried inactivating CCR5 mutations.”
Khalili’s team generated the essential gene-editing constructs, and then applied those constructs in a long-acting slow-release effective antiretroviral therapy (LASER ART) in treated humanized mice, figuring out when to administer the gene-editing therapy and performing testing to maximize HIV. -1 cleavage, CCR5 inactivation, and suppression of viral growth was at UNMC.
In previous work, Gendelman and Khalili’s teams showed that HIV can be eliminated from the genomes of HIV-infected humanized live mice, leading to a cure in some animals.
New dual CRISPR gene-editing strategy holds exceptional promise for human HIV treatment
Although HIV cannot be eliminated by LASER ART in infected mice, the researchers found that maximal suppression of the virus for periods of time measured in months could facilitate the penetration of the antiretroviral drug into viral growth reservoirs. This served to safely maximize viral suppression and control secondary complications of the disease. However, discontinuation of treatment would lead to eventual resurgence of tissue reservoirs and lead to new cycles of rebound infection. HIV integrates its DNA into the genome of host cells and can remain dormant in tissue reservoirs for long periods of time and despite the use of antiretroviral drugs. As a consequence, when ART is suspended even after limited therapeutic times, HIV replication is renewed.
To prevent rebound infection, the researchers began work on next-generation CRISPR technology for the cleavage of HIV, developing a new sistema dual intended to permanently eliminate HIV from the Nebraska animal model.
The new dual CRISPR gene-editing strategy holds exceptional promise for the treatment of HIV in humans. It’s a simple and relatively inexpensive approach,” Khalili says. “The type of bone marrow transplant that has produced cures in humans is reserved for patients who also have leukemia. It requires multiple rounds of radiation and is not applicable in resource-limited regions, where HIV infection tends to be more common.”
Dr. Gendelman’s team carried out experiments in humanized mice treated with LASER ART, which demonstrated that the constructs developed in Temple, when administered together, resulted in viral suppression, restoration of human T cells, and elimination of HIV-1 replication by 58 percent. of infected animals. The findings support the idea that CCR5 has a key role in facilitating HIV infection.
Temple’s team also plans to test the dual gene editing strategy in non-human primates soon.s.
The new dual CRISPR gene-editing strategy holds exceptional promise for the treatment of HIV in humans. “It’s a simple and relatively inexpensive method,” concludes Khalili.
“A few different types of approaches are being explored and in some cases designed to achieve a functional cure for HIV,” says Robert Gallo, who discovered HIV with the Frenchman Luc Montagnier. “One such approach is to use CRISPR technology to destroy the HIV provirus or even a cellular component such as the possibly unnecessary cellular co-receptor for HIV entry.”
#dual #therapy #eliminates #virus #AIDS #mice