The genetic changes that cause the rare, deadly illness known as MOGS-CDG also protect cells from viral infection. Scientists at Temple University’s Lewis Katz School of Medicine have used this exceptional protective ability in a novel gene-editing method aimed at removing HIV-1 infection with no deleterious consequences on cell mortality.
The novel technique, disclosed in the journal Molecular Therapy—Nucleic Acids on April 28th, is based on a combination of two gene-editing constructs, one that targets HIV-1 DNA and one that targets a gene called MOGS—defects in which cause MOGS-CDG. The Temple researchers show that interrupting the virus’s DNA while also purposefully changing MOGS prevents the formation of infectious HIV-1 particles in cells from HIV-1 infected people. The revelation opens up new opportunities for the creation of an HIV/AIDS cure.
Proper MOGS activity is required for glycosylation, a process that modifies various cellular proteins generated in the body to make them more stable and functional. Glycosylation, on the other hand, is used by some pathogenic viruses. Viruses that are enclosed by a viral envelope, such as HIV, influenza, SARS-CoV-2, and hepatitis C, rely on glycosylated proteins to enter host cells.
Lead investigators in the new study were Kamel Khalili, Ph.D., Laura H. Carnell Professor and Chair of the Department of Microbiology, Immunology, and Inflammation, Director of the Center for Neurovirology and Gene Editing, and Director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine, and Rafal Kaminski, Ph.D., Assistant Professor at the Center for Neurovirology and Gene Editing at the Lewis Katz School of Medicine.
Their unique method should have no effect on the health of uninfected cells that retain normal MOGS gene function. In HIV-1 infected cells, stimulation of the apparatus damaged the glycan structure of the HIV-1 envelope protein, resulting in the creation of non-infectious virus particles.
“This approach is conceptually very interesting,” said Dr. Khalili, who is also senior investigator on the new study. “By mitigating the ability of the virus to enter cells, which requires glycosylation, MOGS may offer another target, in addition to the integrated viral DNA for developing the next generation of CRISPR gene-editing technology for HIV elimination.”
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