Genetic Discovery Protects Cells from Viral Infection while Targeting HIV-1

Researchers at the Lewis Katz School of Medicine at Temple University harnessed the protective abilities of genetic alterations linked to a rare, fatal disorder known as MOGS-CDG to develop a new gene-editing strategy for combating HIV-1. Their findings, published in the journal Molecular Therapy – Nucleic Acids, pave the way for potential advancements in the search for a cure for HIV/AIDS.

The team, led by Dr. Kamel Khalili and Dr. Rafal Kaminski, designed an approach combining two gene-editing constructs. One construct targets the DNA of HIV-1, while the other targets the MOGS gene, mutations that lead to MOGS-CDG. By disrupting the virus's DNA and altering MOGS simultaneously, the production of infectious HIV-1 particles is effectively blocked. This groundbreaking technique presents promising possibilities for HIV/AIDS cure development.

MOGS is crucial for glycosylation, a process where certain cellular proteins are modified to enhance their stability and functionality. Interestingly, glycosylation is also utilized by specific enveloped viruses like HIV, influenza, SARS-CoV-2, and hepatitis C to enter host cells. By deliberately modifying MOGS, the researchers disrupted the glycan structure of the HIV-1 envelope protein, ultimately resulting in the production of non-infectious virus particles.

"This approach is conceptually very interesting," says Dr. Khalili, the study's senior investigator. "By targeting both the virus's ability to enter cells, which relies on glycosylation, and its integrated DNA, MOGS presents another potential target for the next generation of CRISPR gene-editing technology aimed at eliminating HIV."

The researchers are conducting preclinical studies to ensure the safety and efficacy of the CRISPR-MOGS strategy. Previous work by the team has successfully demonstrated the removal of viral DNA using CRISPR-based technology in non-human primates. Dr. Khalili, Dr. Kaminski, and Dr. Tricia Burdo, an expert in non-human primate models for HIV-1, are collaborating further to assess the potential of this innovative gene-editing approach.

The novel combined gene-editing-based cure strategy developed by the team holds promise for diminishing HIV-1 spread after antiretroviral therapy (ART) cessation and ultimately eliminating the virus. By disrupting viral entry and editing viral DNA, this approach presents a potential breakthrough in the ongoing fight against HIV/AIDS.