Thursday, November 11, 2010
A vaginal gel that affords both contraception and HIV protection using nanoparticles that carry bee venom is one of the bold, unconventional ideas that won a 2010 Grand Challenges Explorations grant from the Bill & Melinda Gates Foundation.
Grand Challenges Explorations is a Gates Foundation initiative to foster innovative projects in areas where unorthodox thinking is most urgently needed. Recipients receive grants to explore creative solutions to global health issues.
Sam Wickline, MD, professor of medicine, of cell biology and physiology, of physics and of biomedical engineering at Washington University School of Medicine in St. Louis is one of 65 scientists selected in November to participate in the grant program.
Wickline proposes to develop a contraceptive, antiviral gel containing trillions of nanoparticles that will target both HIV and sperm and deliver a bee venom toxin that will incapacitate them.
"Sperm and HIV (the human immunodeficiency virus that can lead to acquired immune deficiency syndrome, or AIDS) are remarkably similar in their natural mechanism of genetic transmission," Wickline says. "Both need to fuse with their target cell in order to deliver their genetic payloads ? DNA in the case of sperm, and RNA in the case of HIV."
Wickline's plan is to use the very means by which sperm and HIV operate to destroy them...
A toxin derived from the substance bees insert into their victims when they sting is the agent that will destroy the sperm and HIV. The toxin, called melittin, comprises more than half of the dry weight of the venom of the honeybee Apis mellifera.
The nanoparticles will carry a synthetic version of the toxin melittin to the targets.
"Cells readily take in melittin," Wickline says. "But once it gets in, it pokes holes in cell membranes destroy the cells."
A local biotech startup company, Kereos Inc., is testing melittin as an anti-cancer agent.
Since melittin can annihilate almost any cell, the trick is to target the melittin to the specific cells intended for destruction (cancer, sperm, HIV) without causing collateral damage to other cells in the body.
Wickline and colleague Paul Schlesinger, MD, PhD, associate professor of cell biology and physiology, attacked that problem two years ago when they developed "nanobees," the name coined for nanoparticles that sequester melittin so that it neither harms healthy tissue nor is degraded before it reaches the intended target.
Wickline and his colleagues have also developed the ability to add agents to the nanobees to cause them to home in on specific target cells. Although nanoparticles are a few thousand times smaller than the dot above an "i," each can carry hundreds of thousands of molecules on its surface...