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‘Molecular Knife’ Shows Promise as New AIDS Treatment

November 10, 1992

LA JOLLA, Calif. (AP) _ Scientists developed a tiny ″molecular knife″ that cuts and destroys part of the AIDS virus, and they soon will test the treatment on people with the deadly disease, a researcher said Tuesday.

″It’s a new technology which could potentially be very powerful, but it needs a lot of refinement,″ said Dr. Flossie Wong-Staal, a researcher at the University of California, San Diego. ″We’re working on it and are very excited about the possibilities.″

Wong-Staal, who earned a national reputation during her tenure at the National Cancer Institute, outlined her research during the 30th annual New Horizons in Science briefing, sponsored by the Council for the Advancement of Science Writing.

AIDS cripples the body’s disease-fighting immune system, leaving patients vulnerable to death from various infections and cancers. To do that, the virus infects certain white blood cells, called T helper cells, then hijacks their genetic instructions so the cells mass-produce more of the deadly virus.

The process kills the original disease-fighting white blood cell and allows new virus particles to spread to more cells and kill them.

The ″molecular knife″ is an enzyme developed by a team headed by Wong- Staal and Northern Illinois University’s Dr. Arnold Hampel. They designed it to cut and destroy genetic instructions used by the AIDS virus, short- circuiting the virus’ ability to reproduce and spread throughout the body.

The researchers applied the enzyme knife to AIDS-infected human white blood cells grown in test tubes. As a result, the virus made only 10 percent to 30 percent as many copies of itself as it normally would have done.

Tests on AIDS patients ″will start within the year″ to learn if the treatment is safe, and later to determine if it is effective in halting or slowing the progression of the deadly disease, Wong-Staal said.

″It’s exciting and should be pursued,″ said Dennis R. Burton, a molecular immunologist at The Scripps Research Institute in La Jolla.

The molecular knife is known as a hairpin ribozyme because it is a hairpin- shaped enzyme made of ribonucleic acid, or RNA. RNA also serves as a genetic blueprint that helps viruses like AIDS reproduce.

Wong-Staal, Hampel and their colleagues obtained the hairpin ribozyme from a potato plant virus, then used chemical reactions to make it latch onto and slice RNA in the AIDS virus, impairing the deadly virus’ ability to reproduce.

A single molecular knife enzyme can cut up the genetic instructions in many AIDS virus particles, increasing its effectiveness.

Wong-Staal said her experiments indicate the hairpin ribozyme works faster and more efficiently than a similar substance, called a hammerhead ribozyme, developed three years ago by researchers at the City of Hope National Medical Center in Duarte, Calif.

Researchers will try to use several of these molecular knives at once, each attacking the AIDS virus’ RNA in slightly different ways, she said. By using several such substances together, reproduction of the virus should be slowed further or perhaps halted.

The major obstacle to use of the molecular knife as a treatment is the need to find an effective way to deliver it to AIDS-infected cells in patients, she said.

One possibility is to put the substance into harmless viruses, possibly including a deactivated AIDS virus, Wong-Staal said. Such viruses would infect the same blood cells that are attacked by the active AIDS virus.

UCSD and Northern Illinois University hold the patent on the new molecular knife. They licensed Biotechnology Research and Development Corp. of Peoria, Ill., to develop it for eventual commercial use in AIDS patients, Wong-Staal said.

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