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Technology Transfer from the University of Oxford

MODIFIED CARBOHYDRATE PROCESSING ENZYMES - Isis Project No 1147

A procedure for modifying enzymes to increase activity and substrate specificity

Marketing Opportunity

There are over 80 therapeutic proteins already in the market generating multi-billion dollar annual sales, however manufacture of these proteins is far from straightforward. Over 70% of all cell-surface human proteins are glycosylated and this is essential for their recognition and function in the human body. The successful production of proteins as therapeutic agents requires either a host cell system that can carry out human-like glycosylation or alternative synthetic methodology for attaching the required sugars to unglycosylated protein.  Although enzymes such as glycosidases have been used in glycosynthesis and are attractive biocatalysts, research has traditionally focused on site-directed mutagenesis alone as a means of modifying glycosidase activity; the construction of mutants is however a lengthy process and it is recognized that having a rapid tool for protein modification would be advantageous.

The fact that there is currently a striking lack of enzymes capable of performing such transformations, shows that there is a clear need for a new protein glycosylation technology that not only allows the creation of pure glycoproteins as potential therapeutics, but does so rapidly.

The Oxford Invention

Researchers at the University of Oxford have developed a method of modifying carbohydrate, processing enzymes such that there is an increase in activity and substrate specificity relative to the unmodified form. The invention uses the combined strategy of site-directed mutagenesis and chemical modification as a means of tailoring the specificity and activity of the enzymes, which may subsequently be used:

  • In glycoside synthesis, trans-glycosylation and glycoside hydrolysis
  • To generate an array of molecules conjugated to carbohydrates
  • To generate glycoproteins – in particular O-linked glycosylations
  • To develop glycoconjugates for use in LEAP (Lectin Directed Prodrug Delivery)

This work is the subject of patent application, and Isis would like to talk to companies interested in developing the commercial opportunity that this represents.

Please contact the Isis Project Manager to discuss this further.

Request Further Information: Project Number 1147 - Modified Carobohydrate Processing Enzymes