Case for Insect Cells
Donald L. Jarvis, Ph.D., professor of molecular biology at the University of Wyoming, made a good case for the baculovirus-insect cell expression system to produce proteins with eukaryotic post-translational modifications, particularly glycosylation.
Insect cell lines, unfortunately, express relatively primitive glycosylation pathways that lack sialylation. Sialic acid groups impart useful pharmacokinetic properties on therapeutic proteins. “Molecules require sialic acid residues to survive the human circulatory system,” explained Dr. Jarvis.
His approach was to isolate genes for the missing glycosylation functions and insert them into insect cells, a technique he calls “strain engineering for glycosylation” or “glycoengineering.”
Ironically this approach is easier in practice than in theory.
“There are many steps in glycosylation pathways. When first thought of incorporating all those genes, of knocking in multiple functions, it seemed mind-boggling,” continued Dr. Jarvis.
That perceived hurdle delayed efforts to glycoengineer insect cells for several years, he concedes. “But when we tried it, we found it to be straightforward.”
His group has efficiently inserted as many as nine unlinked markers into insect cells by simple transfection and co-selection.
“We don’t have to screen more than 40 or 50 clones to find those that express all of these unlinked markers. Insect cell genomes just seem to soak up plasmid DNA,” he said.
In theory Dr. Jarvis could simultaneously transfect for product proteins as well, but he prefers to achieve that with standard baculovirus agents.
When asked “Why not simply use CHO cells, which already sialylate and are known to be robust expression systems,” Dr. Jarvis admits feeling “backed into a corner” when forced into a comparative analysis of expression systems.
“You need a variety of different expression systems in biotech because proteins will be expressed more successfully in one system than another. Biotechnology companies always talk about having four or five platforms in place—E. coli, baculovirus, Pichia, and mammalian cells—to cover their bases.”
Insect cells also provide a safety factor, in that adventitious insect viruses would not infect humans.
Perhaps more controversial is Dr. Jarvis’ contention that on a unit volume and time basis, insect cell culture is less expensive than CHO, and the regulatory issues have become moot. Two approved drugs produced in insect cells have been approved in the U.S: the human papillomavirus vaccine Cerevex, and the prostate cancer immunomodulatory agent Provenge.