Now Available: Humanized Glycosylation in Pichia
RCT has developed improvements to its Pichia Expression Platform that enable the production of proteins with controlled, human-like glycosylation. RCT has assembled these improvements into a new system called Pichia GlycoSwitch®. The technology behind Pichia GlycoSwitch® originates from collaborations with Roland Contreras, Ph.D., Nico Callewaert, Ph.D., and colleagues at Ghent University and the Flanders Institute for Biotechnology (VIB) in Belgium, and BioGrammatics, Inc. in San Diego.
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Pichia GlycoSwitch® Advantages
- Uniform glycosylation: Produces the same type of glycosylation on each protein.
- High-Expression: Expresses glycoproteins at the same high levels seen with Pichia Classic.
- Minimize aberrant glycosylation: Eliminates unwanted glycosylation.
- Customize glycosylation: Allows one to tailor both the amount and type of glycosylation attached to a protein.
- Increased homogeneity of bio-pharmaceuticals: Enables production of proteins with homogenous glycoforms that have the highest therapeutic benefit.
Pichia GlycoSwitch® Technology & Background
The Picha GlycoSwitch® System is based on yeast strains that have been engineered to perform specific glycosylation steps at high fidelity. Many therapeutic proteins are glycoproteins and require the attachment of sugar structures (i.e. glycosylation) to allow for proper folding, expression and biologic/therapeutic activity. Current manufacturing methods based on mammalian cell culture do not allow for the precise control of glycosylation and produce a mixture of different glycoforms, some of which are beneficial and some of which are problematic or of little benefit.
With Pichia GlycoSwitch®, the yeast’s own hyperglycosyl N-glycans are switched to the more human biantennary complex type N-glycans. By mutating the Pichia pastoris OCH1 gene and introducing heterologous enzyme activities, Pichia has been engineered to produce human-like glycoproteins.
Produce High Potency Biologics in Pichia GlycoSwitch®
The Pichia GlycoSwitch® System consists of patents, strains and vectors that are useful for engineering Pichia to make proteins with a number of different, near-homogenous glycoforms. This allows for the identification of the most biologically active glycoforms and creates the opportunity to control and optimize the profile of a final product whether it is used as a therapeutic, a research reagent, or some other purpose. Since, in addition to basic protein function, glycosylation also influences characteristics like pharmacokinetics, stability, bioavailability, and tissue distribution, Pichia GlycoSwitch® technology can be broadly applied to biotherapeutics including growth factors, enzymes, vaccine antigens, fusion proteins, binding domains and monoclonal antibodies. Examples of proteins produced in the Pichia GlycoSwitch®include GM-CSF, IL-10, CH2 domain, IFN-beta, transferrin, and IL-22.