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SAVALnet – Science and Medicine

SAVALnet – Science and Medicine

Functional cure of HIV-1 infection has been documented in three cases. In all of them, treatment of acute myeloid leukemia was by allogeneic transplants of hematopoietic stem cells that harbored heterozygous or homozygous mutations in the HIV-1 CC receptor chemotactic gene type V (CCR5Δ32). Treatment included attenuation of viral infection, the presence of virus-infected cells and tissue reservoirs, and the absence of integrated latent DNA. Measurements of viral reversion were followed by discontinuation of antiretroviral therapy (ART). Current treatment includes both antiretroviral therapy and broadly neutralizing antibodies. Both can reduce, but not eliminate, virus determining latency in CD4+ T cells and mononuclear phagocytes (monocytes, macrophages, and dendritic cells), which represent the major barrier to recovery.

study Louis Katz School of Medicine at Temple University And the medical center of University of Nebraska (UNMC) He shows that a gene-editing treatment that targets two targets — HIV-1, the virus that causes AIDS, and CCR5, the common receptor that helps the virus enter cells — can effectively eradicate HIV infection.

The idea of ​​combining HIV-1 DNA ablation with CCR5 inactivation using a gene-editing technique is based on observations of reported treatments in HIV-infected human patients. In the few cures, patients underwent bone marrow transplants for leukemia, and the donor cells that were used carried inactivating CCR5 mutations.

Dr. Khalili and Dr. Howard E. Gendelman, professor and director of the department of pharmacology and experimental neuroscience at the University of Nebraska Medical Center, were the principal investigators on the new study. They have been collaborating for a long time and have strategically combined their research strengths.

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In previous work, they both showed that HIV can be eliminated from the genomes of live HIV-infected mice, resulting in a cure for some animals. For this research, they combined their expertise in CRISPR gene-editing technology to target HIV-1 with a treatment strategy known as slow-acting, long-acting antiretroviral therapy (LASER), co-developed by Dr. Gendelman and Dr. Benson. Edagwa, Assistant Professor of Pharmacy at UNMC. The laser keeps HIV replication at low levels for long periods of time, which reduces the frequency of ART administration.