Preventive drug for HIV manufactured in plants ready for clinical development
March 30th, 2009
A University of Louisville faculty member at the Owensboro Cancer Research Program (OCRP) has published research that supports the use of transgenic plants in HIV prevention.
The study indicates that growing large quantities of the protein griffithsin in Nicotiana benthamiana — a close relative of tobacco — serves as an affordable, preventive measure for HIV.
Kenneth Palmer, associate professor of pharmacology and toxicology and senior scientist at the James Graham Brown Cancer Center, is senior author of the article “Scaleable Manufacture of HIV-1 Entry Inhibitor Griffithsin and Validation of its Safety and Efficacy as a Topical Microbicide Component” in the Proceedings of the National Academy of Sciences of the United States of America.
The published study was the result of a collaboration between Palmer and the scientists who discovered the drug, led by Barry O’Keefe, Ph.D., at the National Cancer Institute. Two Kentucky biotechnology companies, Intrucept Biomedicine, LLC, and Kentucky Bioprocessing, and scientists at Duke University and the University of London in the United Kingdom also participated in the study.
“This drug works by binding to sugar molecules on the surface of HIV, preventing the virus from infecting cells of the immune system.” O’Keefe said. Using plants to produce griffithsin will offer underdeveloped countries with an affordable solution for prevention of HIV transmission.”
According to Palmer, when manufactured in the form of a microbicide gel or film for topical application, the product’s selling price could compare to that of male condoms.
HIV research is a focus of OCRP as contracting HIV increases risk for cancer.
The researchers modified the tobacco mosaic virus to incorporate the griffithsin gene and infected more than 9,300 plants, extracting enough griffithsin to produce about 100,000 HIV microbicide doses from the leaves. The chemical performed identically to griffithsin produced by other methods. In a petri dish model incorporating cervical tissue, it strongly inhibited HIV and did not induce markers of inflammation; a standard animal test confirmed it was not a chemical irritant.
Many HIV entry inhibitors are biological molecules, making them virtually impossible to produce by a purely chemical process and requiring synthesis by living organisms. In comparison with cell-culture based manufacturing processes, plant-based manufacturing of biologicals offer significant cost savings by reducing the need for expensive infrastructure for growing organisms to produce the protein, and also provide the economies of scale offered by agricultural production.
Other Owensboro authors of the study include Barry Bratcher and Steven Hume of Kentucky BioProcessing. The company, which specializes in the expression, extraction and purification of proteins and other high value products from plants, will manufacture proteins for the drug for in future clinical trials.
Owensboro Medical Health System and the UofL’s James Graham Brown Cancer Center created OCRP as a joint venture to develop cancer therapies using plant-based production systems. Four UofL faculty members conduct their research in laboratories maintained by OMHS at the Mitchell Memorial Cancer Center in Owensboro.