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Genetic engineering can make the cells of our immune system resistant to infection by the human or monkey immunodeficiency virus (HIV and SIV, respectively). Recent data shows that treatment with HIV-resistant immune cells has shown encouraging results in patients.
And now, researchers have found ways to make large numbers of virus-resistant immune cells from monkeys, allowing for the design of future studies on the safety and efficacy of immune therapy in a preclinical animal model.
This encouraging research will help scientists consider alternative approaches to treating HIV, the virus that causes AIDS.
It is estimated that there 37.7 billion people infected with HIV. Medications are effective in suppressing the replication and transmission of the virus, but they are necessary throughout life and often cause side effects and cannot completely eliminate the virus from the body.
HIV especially infects and kills certain immune cells called T cells, progressively weakening the patient’s immune system and increasing susceptibility to infections and certain types of cancer.
One potentially effective way to eliminate infected cells and restore lost T cells is immunotherapy, in which patients’ own T cells are genetically modified in the laboratory to make them resistant to HIV infection and then returned to HIV. the patients.
However, only a limited number of genetically modified T cells can be produced, and procedures for isolation, modification, expansion, and reinfusion of T cells can compromise their functionality and survival.
An alternative way to produce T cells in large numbers is to do so from dand induced pluripotent stem cells (iPSC), which are rapidly replicating immature cells that can be produced from patients’ blood or skin cells.
iPSCs can be grown in the laboratory in large numbers, genetically modified, and subsequently converted into T cells, thus generating a large number of patient-specific T cells.
To test this hypothesis, the team at the Faculty of Medicine and Public Health of the University of Wisconsin-Madison that coordinates Igor Slukvin worked on a preclinical model to generate and test genetically modified T cells derived from monkey iPSCs at the Wisconsin National Primate Research Center.
The results are published in Cell Stem Cell
Using the gene-editing tool, CRISPR/Cas9, the researchers deleted the gene that encodes a specific protein called CCR5, which is required for viral entry into T cells.
Monkey iPSCs with CCR5 deletion became T cells and attacked simian immunodeficiency virus (SIV), a virus closely related to HIV. These engineered T cells were protected against SIV infection, whereas T cells with intact CCR5 could be easily infected.
The concept that the immune cells of a person with HIV can attack HIV without being susceptible to the virus it is not new. since in 2008 Timothy Ray Browna patient with acute myeloid leukemia and HIV infection, received a bone marrow transplant in Berlin from an unrelated donor whose blood stem cells had the genetic variant CCR5 Delta 32 and was cured, therapies based on bone marrow transplantation have won force and researchers are trying to replicate this phenomenon, although allogeneic transplants, such as the «Berlin patient» carry a high risk of mortality and require long hospital stays and are not a practical solution for HIV patients who do not have blood cancers.
Currently there are many approaches that have been aimed at identifying cells with this variant and now the fact of being able to design laboratory cells is a big step.
Monitoring of these animals will show whether the cells T sin CCR5 derived from iPSCs can survive and function in monkeys infected with SIV, with the ultimate goal of controlling or even eliminating the viral infection.
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