CropTech Development Corp., a fledgling biotechnologycompany in Blacksburg, Va., is gearing up to geneticallyengineer oral vaccines in plants for the U.S. army.
Plant cell biologist David Radin, CropTech's president,told BioWorld Today that the six-month, $99,544 SmallBusiness Innovative Research (SBIR) contract with thearmy's Medical Acquisitions Research branch in Ft.Detrick, Md., will test the feasibility of cloning the genesfor anthrax and plague bacterial surface antigens inNicotiana tabacum, the common tobacco plant.
Late last month in Minneapolis, CropTech's vicepresident for research, Carol Cramer, told the AmericanSociety of Human Genetics 1995 annual meeting that she,Radin and their co-workers had expressed the humanglucocerebrosidase gene in transgenic tobacco plants.
Described as "the world's most expensive drug," Radinobserved, human glucocerebrosidase (hGC) is usedtherapeutically to reverse the build-up of cerebrosidelipids in Gaucher's disease. Genzyme Corp., ofCambridge, Mass., produces commercial hGC fromhuman placentas. Its cost to Gaucher's patients and theirthird-party payers runs from $150,000 to $400,000 a year.(See BioWorld Today, March 3, 1995, p. 1.)
"Between 2,000 and 8,000 placentas," Radin pointed out,"are needed to produce one dose of the drug, which mustbe administered every two weeks."
"As an alternative source of enzyme for therapy," Cramerreported, "we have evaluated transgenic tobacco plantscontaining the recombinant human glucocerebrosidasecDNA." Using Agrobacterium tumefaciens as a vector,she transferred the coding sequence with its induciblepromoter into the plant's genome.
"With differing levels of induction and cDNA copynumber," Cramer said, "the human glucocerebrosidaseglycoprotein was stably expressed at levels from less than0.5 to more than 1.6 milligrams per gram fresh weight ofleaf. This," she added, "translates into about 1.6 grams ofcrude hGC per typical mature tobacco plant."
A single tobacco plant, Radin said, "can produce enoughof the enzyme for one dose of drug, at least. Sucheventual therapeutic use," he added, "[would come] atpotentially much reduced costs."
On Oct. 3, 1995, Cramer made a similar report to theInternational Symposium on Genetically EngineeredPlants for Commercial Products and Applications,meeting in Lexington, Ky. There she explained that shehad chosen tobacco as CropTech's "initial transgenicsystem because Agrobacterium-mediated transformationis highly efficient, its prolific seed production greatlyfacilitates biomass scale-up, and development of new`health-positive' uses for tobacco has significant regionalsupport."
Enlarging on this potential repositioning of the South'smain cash crop, Radin observed that "tobacco couldbecome beneficial, rather than hazardous, to one'shealth."
He said that validating the Gaucher therapeutic enzymefor human trials would take another 18 months or so, andthat his company has other lysomal storage-disease drugson its N. tabacum drawing board.
It has already cloned human protein C (hPC) at low levelsin tobacco leaves. "Although tobacco-derived hPC hasnot yet been tested for all post-translationalmodifications," Cramer told her Kentucky audience, "orfor anti-clotting enzymatic activity, these results arepromising. They suggest considerable conservation ofprotein processing machinery between plants andanimals." (See BioWorld Today, Nov. 13, 1995, p. 1.)
CropTech, Radin explained, is a spin-off from theVirginia Polytechnic Institute and State University inBlacksburg. He and Cramer were both faculty there, inthe department of plant pathology and physiology, whereshe remains.
CropTech is sole licensee of "a proprietary, promoter-based expression system for stable integration of genes ofinterest into plant genomes, which is our uniquecontribution," he said, for which the University has apatent pending. Cramer is principal inventor.
The company occupies premises in Virginia Polytech'sResearch Park, adjacent to the campus. So does anotherbiotech spin-off, originally TransPharm Inc. Now asubsidiary of the Scottish firm, PPL Therapeutics Ltd., itgoes by the name PPL Therapeutics Inc., and issynthesizing high-value proteins in the milk of pigs,rather than in plants. Its parent company, in Edinborough,is doing the same in sheep. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.