Engineering of carbohydrate processing enzymes for generation of therapeutic glycoproteins with increased serum halflife

Biopharmaceuticals are molecules produced using biotechnology, rather than chemistry, for therapeutic purposes. Biotechnology uses microorganisms (such as bacteria or yeasts) or biological substances (such as enzymes) to manufacture pharmaceutical compounds. Many biopharmaceuticals are very large proteins, which show considerable promise in the treatment of a wide range of diseases. Unfortunately, owing to the complex mechanisms that the body requires to regulate its own proteins in the bloodstream, foreign proteins in the form of medicines are typically rapidly destroyed or removed from the circulation by the body. Sugars found on the surface of mammalian proteins protect provide protection from destruction by circulating protein-degrading enzymes. They also provide a signal when it is time for a protein to be removed from the blood. Dr. Jamie Rich is investigating whether adding specific sugars to protein drugs could help them last longer in the bloodstream and be more effective. He is working to develop an enzyme that can “build” a particular type of sulphur-containing sugar onto the surface of the protein drug. This promises to protect the protein from degradation, prevent the exposure of sugar-based clearance signals, and allow the protein to function normally as an effective long-lasting drug. Creating longer-lasting drugs would reduce the required amount and frequency of dosages, resulting in reduced drug costs. If successful, this approach could be applied to a wide range of proteins that are currently used as drugs or are in the drug development stage.