CRISPR Identifies Potential Gene Targets to Hobble HIV Infection

From Scientific American:

In research published Tuesday in Cell Reports, scientists announced that they had used CRISPR/Cas9 to test gene after gene after gene in human immune system cells—45 genes in all, sometimes simultaneously and sometimes individually—to identify those that have anything to do with infection by theHIV virus, which causes AIDS when it infiltrates those T cells.

For years, scientists have known that mutations in some genes can keep HIV from getting inside T cells (editing genes to create that protective mutation is being tested in a clinical trial). But it never hurts to find more ways to block HIV infection, scientists at the University of California, San Francisco, and its Gladstone Institutes figured.

Enter CRISPR/Cas9, which is so easy to use that even small labs are jumping into the CRISPR pool in a way they couldn’t with the previous generation of genome-editing tools.

When scientists want to edit scores of genes to see which changes protect T cells against HIV, they need to build a separate CRISPR/Cas9 assemblage of multiple molecules each time. Because that’s so easy, the UCSF scientists marched through the genome in human T cells like ants marching across a picnic spread: a project that would take years with the previous generation of genome editing tools instead took months.

Using a clever way that some of the same researchers invented last year to get CRISPR/Cas9 into cells—a jolt of electricity makes cells open their entry gates—they sent one CRISPR complex after another—149 in all—into hundreds of thousands of T cells isolated from the blood of healthy volunteers.

After each edit, the scientists, co-led by UCSF/Gladstone medical geneticist Nevan Krogan and immunologist Dr. Alexander Marson, tested the now-mutated T cells to see if they kept HIV out entirely, kept it from insinuating itself into the T cell’s genes (which is how the virus replicates), or otherwise …

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