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Switch On Your HIV Smarts.

Turning “off” these 3 genes would protect T cells from HIV

, by Emily Newman

DNA geneA team of researchers at the Ragon Institute of MGH, MIT and Harvard and the Broad Institute of MIT And Harvard have recently identified human genes that could be the key to a gene therapy-based HIV treatment.

Using a technique called CRISPR-Cas9, the researchers scanned the genes of human T cells (the cells that are primarily targeted and invaded by HIV) to identify genes that enable the cells to be infected by HIV.

“Viruses are very small and have few genes—HIV has only 9, while humans have more than 19,000—so viruses commandeer human genes to make essential building blocks for their replication. Our goal was to identify human genes, also called host genes, that are absolutely essential for HIV to replicate but could be eliminated without harming a human patient,” said Bruce Walker, MD, director of the Ragon Institute and co-corresponding author of the article published in Nature Genetics.

In addition to identifying two previously known genes (CCR5 and CD4), the researchers identified three new genes. Two are involved in the production of enzymes (TPST2 and SLC35B2) that help the virus attach to the T cell, and one (ALCAM) is involved in cell-to-cell adhesion. Importantly, none of these genes are essential for cell survival. So future gene therapies or treatments—that inactivate these genes—could have the potential to protect CD4 cells from HIV infection without killing these immune system cells entirely.

A benefit to HIV therapies that target human T cells—instead of the virus—is that the therapies would not be affected by drug resistance, explained Ryan J. Park, the co-author of the article. “Because HIV mutates so rapidly, drug-resistant strains frequently emerge, particularly when patients miss doses of their medication. Developing new drugs to target human genes required for HIV infection is a promising approach to HIV therapy, with potentially fewer opportunities for the development of resistance.”

Although this research has identified three promising targets for future HIV therapies, gene therapy “remains a challenging and potentially costly therapeutic approach,” explained Park.

Read more about the successful cell and gene therapy treatment that led to an HIV cure for Timothy Ray Brown, the “Berlin Patient.”

Source

Park, R.J. and colleagues. A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Nature Genetics, December 2016.

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