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Researchers successful at blocking HIV from healthy cells

By Mary Ann Roser

Austin American-Statesman

Published: Friday, Jan. 25 2013 11:15 p.m. MST

AUSTIN, Texas (MCT) — Researchers at the University of Texas and Stanford University have blocked HIV from invading healthy cells in the laboratory, saying the work could lead to treating patients without drugs.

The scientists knocked out a gene involved in HIV and inserted three genes that help the cells resist the virus in a process they call "targeted stacking." The research was published this week in the journal Molecular Therapy.

The process is three to five years away from being tried in humans and mirrors recent strategies to attack HIV, the precursor to AIDS, at the genetic level. But the UT and Stanford scientists said their method is more precise — and more effective.

It combines two different approaches — using a zinc protein to inactivate an HIV gene and then adding blockers to fight off both types, or strains, of the virus.

These "zinc-finger nucleases" act like "a molecular scissors that can be used to cut out a gene in the human genome, and insert other ones in its place," said Sara Sawyer, a co-author of the study and an assistant professor of molecular genetics and microbiology at UT-Austin. "That is exactly what we did. We cut out a gene that HIV needs, and replaced it with three genes that work to block HIV replication. This makes T-cells virtually resistant to HIV infection, at least in the lab."

Her collaborator at Stanford, Dr. Matthew Porteus, said, "It's like a Reese's Peanut Butter Cup. We're fusing two approaches."

Such gene manipulations represent the next wave of HIV research and "could contribute toward a cure for HIV," said Dr. Paul Spearman, a research professor and vice chairman for research in the Department of Pediatrics at Emory University in Atlanta.

"It's a clever way of enhancing the ability of zinc nucleases in blocking HIV infection," said Spearman, who isn't involved with the UT and Stanford team. "It's a really promising approach."

The research builds on work done by Sangamo BioSciences Inc. in Richmond, Calif., which is conducting two human trials that involve taking cells from patients, cutting out a gene that is critical for HIV infection and returning the cells to the patients, without adding HIV blocker genes.

"I would argue that the pure gene knock-out approach is more precise," said Philip Gregory, Sangamo's vice president for research and chief scientific officer. And it's simpler than adding genes to an altered cell, he said.

"We think it's a much easier argument to take away something that is permanent — because it's a genetic change — and should add no further burden to the cell," Gregory said. He added that the trials are going well and by year's end should produce answers on whether the process works.

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