High-throughput CRISPR gives T cells a fighting chance against HIV

h.i.v. infected t cell

A team at the University of California in San Francisco has brought a large-scale version of CRISPR gene editing to the fight against HIV infection, offering possibilities for both the discovery of new techniques and the ability to treat those with the virus.

The researchers at UCSF developed a high-throughput CRISPR platform to modify the genes in immune cells to defend them against HIV. As they test different editing methods, they hope to home in on the combination that will protect the donated cells.

The concept came about from the study of people who are naturally unsusceptible to HIV, a very small group whose genetic resistance has given scientists a place to start when editing immune cells for the use in HIV-laden patients.

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"There have been lots of efforts to sequence the genomes of resistant people to discover the mutations that make them immune to the virus," lead author Judd Hultquist said. "But there are many different genes that could be involved: some control the virus's ability to enter immune cells, others control how the virus tricks cells into expressing its genes. Until now, there was no way to test which of these mutations actually confer resistance in primary human T cells."

The new system is automated and can mutate genes on the scale of hundreds of thousands of T cells at high speeds. The speed is a crucial point because T cells are very fragile outside the human body, so donated immune cells are edited quickly and the CRISPR machinery breaks down shortly thereafter to avoid further changes.

"If we want to start editing T cells and putting them back into people as a therapy," co-author Nevan Krogan said, "I think this will be the gold standard for how to do that quickly, safely, and efficiently."

The team says this is just the tip of the iceberg, too, as the technique could have broader implications among infectious diseases other than HIV.

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