Designer Molecules: Engineering a Better Approach to HIV Treatment

	Thomas Griffin

Ravi Kane, assistant professor of chemical engineering, is designing new molecules that may one day fend off an HIV infection. Bolstering the body’s molecular defenses is a novel method that may lead to highly effective treatments for HIV, the virus that can lead to AIDS.

Kane has received a two-year, $150,000 grant from the National Institute of Allergy and Infectious Disease (NIAID), a division of the National Institutes of Health, to pursue research into this promising HIV treatment.

Today’s FDA-approved HIV treatments take aim at the virus itself. Drugs used in the standard “cocktail” regimens, including reverse transcriptase and protease inhibitors, are intended to disable HIV at two stages in its replication process. Such treatments are undoubtedly lifesaving for many people; however, they deliver varying success due to the ongoing emergence of resistant HIV strains. These drugs are also expensive and lead to a host of side-effects, including lipodystrophy (abnormal fat accumulation or loss in certain parts of the body) and dangerously high cholesterol and triglyceride levels.

Kane’s research team at Rensselaer, and Albany Medical Center collaborators Kathy Stellrecht and Dennis Metzger, are trying a different approach. The Rensselaer team is designing molecules that block the particular receptors (located on human cells) that act as the docking sites where the majority of HIV strains make their first attempt at infiltration. These receptors are present all over the cell surface, requiring a molecule with a “multi-armed” (or multivalent) structure to do the best job of preventing a virus from docking.

“Multivalency allows us to block more than one receptor with each molecule,” says Kane. “This approach has the potential to be very effective — in fact, orders of magnitude more effective than any existing treatment.”

There are multiple benefits to treating HIV by blocking its entrance to human cells. In contrast to the constantly mutating virus cells, the human receptors are stable and do not change over time, making development of resistance to a blocking drug unlikely. In addition, the new entry inhibitors may be extremely effective without any dangerous side-effects. People with a genetic defect (a natural blockage) in this receptor show immunity to HIV infection, but are otherwise normal. The researchers admit that this preliminary research is very exciting; however, further study and testing will be needed to develop a viable treatment.

“We hope the next two years of work will form the basis of a more detailed grant in the future,” says Kane.