"For the past 20 years, gene therapy has been hampered by the lack of a good carrier for therapeutic genes that can travel through the blood and aim itself at a precise location, thereby minimizing harmful side effects," explained Irvin S.Y. Chen, Ph.D., director of the UCLA AIDS Institute. "Our approach proves that it is possible to develop an effective carrier and reprogram it to target specific cells in the body."
The UCLA team employed a two-step approach to transform HIV into a cancer-seeking machine. First, the scientists used a version of HIV from which the viral pieces that cause AIDS had been removed. This allowed the virus to infect cells and spread throughout the body without provoking disease.
"The disarmed AIDS virus acts like a Trojan horse transporting therapeutic agents to a targeted part of the body, such as the lungs, where tumors often spread," said Chen, a professor of medicine, microbiology, immunology and molecular genetics and a member of the Jonsson Comprehensive Cancer Center at the David Geffen School of Medicine at UCLA.
Second, the scientists stripped off HIV's viral coat and redressed it in the outer suit of the Sindbis virus, which normally infects insects and birds. By altering the Sindbis coat, they reprogrammed the AIDS virus, which ordinarily infects T-cells, to hunt down and attach to P-glycoproteins -- molecules located on the surface of many cancer cells. The UCLA team is the first to prove that modified HIV will target and bind with P-glycoproteins.
"P-glycoproteins cause big problems by making the cell resist
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Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California - Los Angeles
13-Feb-2005