Gene technology is widely used for the industrial production of pharmaceuticals. The demand for suitable expression systems is increasing as emerging systematic genomics result in an increasing number of targets for the various industrial branches. The production of recombinant proteins has to follow an economic and qualitative rationale, which is dictated by the characteristics and the anticipated application of the product compound. The methylotrophic yeast Hansenula polymorpha provides an expression system with superior characteristics for a wide range of industrial applications.

Gene sequences encoding the desired proteins - for instance, that of a hepatitis B antigen - are fused to strong, inducible promoter elements derived from genes of the methanol metabolism pathway and integrated into the transformation plasmids. Upon transformation the newly acquired plasmids that are mitotically stable are integrated into the H. polymorpha genome. The resulting recombinant strains harbor many copies of the heterologous DNA. This high copy number and the selection of the strong inducible promoter element provide a high reproducible industrial scale production of the desired protein. Depending on the genetic components a protein can be secreted or intracellular deposited.

Crucell’s H. polymorpha patented technology is a broadly applicable protein expression system. It offers a safe and robust platform for industrial scale production of pharmaceuticals including vaccines. In areas where Crucell is not using the H. polymorpha technology for its own product development, the company licenses the technology to others.

The H. polymorpha platform has been successfully applied to the process development of pharmaceuticals such as the hepatitis B vaccine Hepavax-Gene^®, feed and food additives. The expression system has proven to be a safe, reliable system for a broad range of industrial proteins.