Stanford School of Medicine engineers HIV resistance through genes

Feb. 8, 2013, 2:02 a.m.

Correction: In a previous version of this article, The Daily incorrectly stated Sara Sawyer’s university affiliation and incorrectly described the technique used to create the hybrid gene. The Daily regrets these errors. 

A Stanford School of Medicine researcher has discovered an innovative way to engineer immune system cells to resist H.I.V. infection. The breakthrough has the potential to ultimately assist the development of gene therapies meant to counter the virus.

Matthew Porteus M.D. ‘94 Ph.D. ‘94 focused his research on altering genes’ proteins to prevent the virus from attaching to T-cells, which are specialized immune cells. His team—which included University of Texas Austin Professor of Molecular Genetics and Microbiology Sara Sawyer and M.D./Ph.D. candidate Richard Voit—used a technique called homologous recombination to increase resistance via small cell mutations.

“We are trying to give the T-cells a new property,” Porteus said. “Normally they are not H.I.V. resistant, and what we are doing is changing their DNA so that they become H.I.V. resistant.”

While the technique used a hybrid gene created by combining part of a Rhesus monkey gene with part of a human gene, Porteus downplayed the significance of the limited usage of monkey genes.

“What we’re honestly worried about is if we put entire monkey genes into humans then the body will recognize them as foreign and reject them,” he said. “That’s why like we like to use the hybrid gene, where only a tiny portion of the gene is from the monkey.”

Voit, who began working with Porteus in 2008, said that the team’s discovery was stimulated by merging the specialties of Porteus’ and Sawyer’s labs.

“It was actually pretty fortuitous set of circumstances. At Matt’s lab, a focus of research has been strategically modifying the genome itself,” Voit said. “The other side of it was Sara Sawyer, whose lab is discovering new immune mechanisms that protect cells against H.I.V.”

Voit, Sawyer and Porteus began working together in 2008 after Porteus, who was teaching at University of Texas Southwestern, visited UT-Austin to give a seminar. A collaborative partnership formed, and the team applied technologies developed at Stanford to genes discovered at UT-Austin.

“My lab is interested in finding new treatments for diseases like thalassemia and sickle cell disease and such,” Porteus said. “Out of that work, we have gotten really good at modifying a genome.”

Sawyer said that, when she met Porteus, the two realized that his work could be applied to H.I.V. as well.

“We talked about how his approach may be useful to treat H.I.V./AIDS patients,” she said. “We came up with this crazy idea and never thought that we would pursue it.”

Though Sawyer believes their discovery could eventually be used to treat patients, she predicted it would be a long time before this opportunity is available.

“I’m sure it won’t happen as soon as I would like it to,” she said. “The standards are so high. So far, this is only working in the lab, but the idea ultimately is to make T-cells resistant to H.I.V. and reintroduce them into a patient’s body.”

Nitish Kulkarni '16 is a senior majoring in Mechanical Engineering. He writes about technology and breaking news, and runs online content sections. Email him at nitishk2 'at' stanford.edu.

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