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Immune cells engineered in lab to resist HIV infection, Stanford study shows
Date:1/22/2013

e CCR5 and CXCR4 receptors. The disabling of the CCR5 gene by the nuclease, as well as the addition of the anti-HIV genes, created multiple layers of protection.

Blocking HIV infection through both the CCR5 and CXCR4 receptors is important, Porteus said, as it hasn't been achieved before by genome editing. To test the T cells' protective abilities, the scientists created versions in which they inserted one, two and all three of the genes and then exposed the T cells to HIV.

Though the T cells with the single- and double-gene modifications were somewhat protected against an onslaught of HIV, the triplets were by far the most resistant to infection. These triplet cells had more than 1,200-fold protection against HIV carrying the CCR5 receptor and more than 1,700-fold protection against those with the CXCR4 receptor, the researchers reported. The T cells that hadn't been altered succumbed to infection with 25 days.

Porteus said he views the work as an important step forward in developing a gene therapy for HIV.

"I'm very excited about what's happened already," he said. "This is a significant improvement in that first-generation application."

He said a potential drawback of the strategy is that while the nuclease is designed to create a break in one spot, it could possibly cause a break elsewhere, leading to cancer or other cell aberration. He said it's also possible the cells may not tolerate the genetic change.

"It's possible the cells won't like the proteins they're asked to express, so they won't grow," he said.

But he said he believes both problems are technically surmountable. He said the researchers' next step is to test the strategy in T cells taken from AIDS patients, and then move on to animal testing. He said he hopes to begin clinical trials within three to five years.

Though the method is labor-intensive, requiring a tailored approach for each patient, it would save patients from a life
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Contact: Ruthann Richter
richter1@stanford.edu
650-725-8047
Stanford University Medical Center
Source:Eurekalert

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