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Stealth drug idea snags Gates Foundation support

November 12, 2008 By Terry Devitt

A proposal to create a stealth drug, one that remains cloaked inside a cell until activated by a pathogen, has snared a high-profile $100,000 award from the Bill & Melinda Gates Foundation.

UW-Madison biochemist Ron Raines‘ proposal to the Gates Foundation’s Grand Challenges in Global Health initiative beat 40-to-1 funding odds and is aimed broadly at developing therapeutic agents that limit drug resistance.

The idea floated by Raines and his group involves creating a novel cytotoxin, an agent poisonous to cells, from an enzyme known as a ribonuclease whose job is to cleave RNA. By making an inactive precursor form of the RNA-slicing enzyme, Raines says, it’s possible to deliver the agent to cells where it can reside benignly until activated by a pathogen such as HIV.

In the case of HIV infection, the cloak, Raines explains, is removable only by a protein-slicing enzyme that the pathogen requires to complete its life cycle. “As that cleavage can only occur in cells infected with the HIV-1 virus, the toxic activity of the ribonuclease will be unleashed only in infected cells.”

A therapy that kills only HIV-infected cells has the potential to eradicate in patients the reservoir where the virus does its dirty work. The strategy, Raines adds, could also be used as a prophylactic, preventing the virus from getting a foothold in the cells it commandeers to make new virus particles.

The approach, according to Raines, could also be used to develop strategies for combating pathogens in addition to HIV.