A highly efficient and flexible protein production technology

Gene expression technology is widely used for the industrial production of healthcare products. The demand for suitable expression systems is increasing as systematic genomics research methods produce an increasing number of targets for the various industrial sectors. The production of recombinant proteins must follow an economic and qualitative rationale that is dictated by the characteristics and the anticipated application of the product. 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, a hepatitis B antigen (protein eliciting an immune response)—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 Hansenula 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 highly reproducible, industrial-scale production of the desired protein.
 

Availability

Crucell’s patented Hansensula polymorpha 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 Hansensula polymorpha technology for its own product development, the company licenses the technology to others.

Experience

The Hansenula polymorpha platform has been applied successfully to the process development and manufacture of pharmaceuticals, such as Crucell’s hepatitis B vaccine Hepavax-Gene® and interferon alpha2a, and to the production of enzymes approved as food or feed additives. The expression system has proven to be a safe, reliable production platform for a broad range of industrial proteins.