Hybridons: Major Research Advance Rumored; Call for Information

A well-informed source recently told us that researchers are excited about a designer drug being developed by major pharmaceutical companies. We have NOT been able to confirm this report, but chose to publish what we heard, in case any of our readers have more information about this project and can help us assemble a complete picture.
Apparently scientists prepared a mirror image of part of the "tat" gene of HIV--a gene which regulates the activity of
the virus. This chemical was then attached to a sulfate group to make it water soluble. In this form, according to the
report, it enters every cell, and shuts down HIV, with little toxicity to the cell.
The drug has not yet been tried in humans. But according to our source, the same idea was applied to a form of mouse leukemia caused by a virus, and it did work; when given to mice, the mouse version of the drug arrested the disease.
A paper on this technology, called "hybridons", was published two years ago (Zamecnik and others, 1986). It has
not received much attention, perhaps because the idea of a designer drug which enters cells and blocks a specific gene seems futuristic, not something imminent. Yet that early paper reported HIV inhibition up to 95 percent in cells in the laboratory, and suggested that the approach seemed useful for treating patients with AIDS or ARC.
What may be new, according to the report we heard, is that this approach has worked in mice, and is generating much
excitement among the professionals who know about it. This technology could apply also to cancer, certain genetic defects, and other retroviral diseases, as well as AIDS.
Apparently the drugs are fairly easy to make, with a specialized machine called a DNA synthesizer. But there are
billions of different possible chemicals of this class, and most would be ineffective or harmful.
If you have any other information about hybridons or any related project, please call or write John S. James, (415) 255- 0588, or P.O. Box 411256, San Francisco, CA 94141.

References

Goodchild J, Zamecnik PC, Gallo RC, and Sarin, P. Inhibition of Expression of Human T Lymphotropic Virus Type III
Proteins in T Cells by Anti-Sense Oligodeoxynucleotides (Hybridons). Federation Proceedings volume 45 number 6, page 1752 (abstract only), 1986.
Zamecnik PC, Goodchild J, Taguchi Y, and Sarin PS. Inhibition of Replication and Expression of Human T-cell
Lymphotropic Virus Type III in Cultured Cells by Exogenous Synthetic Oligonucleotides Complementary to Viral RNA.
Proceedings of the National Academy of Sciences USA, volume 83 number 12, pages 4143-4146, June 1986.

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