Man Cannot Live on Science Alone
Every transgenics company has wonderful science, but successful pharmaceutical companies do not live by science alone. To persevere companies must focus on products, not technology. And it pays to operate in large, hot therapeutic areas like diabetes.
In November of last year, SemBioSys Genetics (www.sembiosys.com)announced proof-of-concept for a plant-produced insulin, using the companys Stratosome expression system. A study, published in the January 2006 edition of Plant Biotechnology Journal, described insulin production in the seeds of the plant Arabidopsis thaliana.
According to CEO, Andrew Baum, plant-based production could reduce capital costs for an insulin facility by 70%, and cost-of-goods by more than 40% compared with current production methods. The next step, says Baum, is to express the peptide in safflower, the SemBioSys commercial production system of choice.
Stratosome expresses proteins in plant seeds, attaching them to oily molecules, naturally occurring in seeds. Proteins are stable in that form more or less indefinitely. Purification is simplified by the separation of the oily structures from homogenized seeds. Similar oil-protein structures may be used to deliver protein drugs by mouth.
Greenovations (www.greenovation.com) moss bioreactor is reminiscent of the Biolex Lex expression system, but there are many differences. Instead of intact plants the expression system is cultured, suspended cells of the well-characterized Physcomitrella patens moss. Physcomitrella can be made to glycosylate proteins in human-like fashion, which reduces concerns about immunogenicity. In addition, the cultures are easily scaled to several thousand liters. Since proteins are excreted into the medium, downstream purification is easier than with mammalian cell cultures.
According to the company, ion exchange is typically the first step. And, since it is a continuous system, high yields are possible —up to 30 mg/L per day. In October, 2005, the company introduced a polyethylene glycol-mediated transient gene expression system for gene expression in moss with or without the use of viral or agrobacterial vectors.
Transgenic plant biotechnology relies on either stable genetic transformation or transient infection by viral vectors. Although transient expression is much faster, it has been limited by viruses low-infectivity and their small transgene-carrying capability.
Last year, Icon Genetics(www.icongenetics.com) published a paper in Nature Biotechnology on a novel transient gene expression system for plants. Icons method uses Agrobacterium as the infective agent for viral replicon delivery, which introduces the gene of interest in all mature plant leaves simultaneously, leading to high gene expression levels. According to the company, indefinitely scalable transfection method is rapid, achieves high yields, and is capable of human-like post-translational glycosylations. The companys first-generation platform achieves up to five g per kg of biomass after only one to two weeks of cultivation. Bayer acquired Icon in January.