Penn gene therapist unveils potential HIV weapon

In a feat that is renewing hopes for conquering AIDS, researchers have genetically engineered vital immune cells to make them resistant to HIV infection.

To confer this invulnerability, scientists took the immune cells, called T cells, from HIV-positive patients' own blood, then snipped out a single gene - the first time such a precise alteration has been achieved on a meaningful scale.

Put back into the patients, the modified T cells were no longer able to make a particular protein that HIV grabs - like a molecular door knob - to enter the cells that it ravages.

At an AIDS conference in Boston on Wednesday, University of Pennsylvania gene therapy expert Carl June presented data from nine HIV-positive patients who received the novel treatment in Philadelphia, New York, and California beginning in July 2009.

The engineered cells not only defied HIV infection in all nine patients, the cells multiplied dramatically in eight patients - in one case, accounting for six percent of the patient's total T cell supply. In addition to the blood, the T cells were found in tissue in the patients' guts, an area of the body where HIV builds a reservoir.

June, who has worked on other experimental gene therapies for HIV, said the new approach "shows the most promise of any yet tested."

"It's a big accomplishment because this is the first successful attempt at genetic editing," he said. "It gives us an essential tool."

That tool - called "zinc fingers" because an atom of zinc binds to two loops of proteins - has been developed by Sangamo Biosciences of Richmond, Calif., the small biotech company that is funding human testing of the engineered T cells.

Zinc fingers are able to recognize specific sequences of DNA. By attaching a protein that cuts DNA, scientists can use zinc fingers like molecular scissors, cutting and then deleting - or inserting - genes. Until now, gene therapy has been imprecise, relying on viruses to insert genes somewhat randomly into a cell's DNA.

"This is elegant work, scientifically very sound, and an important 'proof of concept,'" said Anthony Fauci, an AIDS research pioneer at the National Institutes of Health, which funded the lab research that laid the groundwork for the human studies.