Production and commercialization of human glycosylation enzymes for chemistry and biology

PROJECT SUMMARY Cell surface and secreted glycoproteins and glycolipids play critical roles in cellular physiology and pathologybut challenges remain in understanding how glycan based reagents can be leveraged for biochemical and therapeutic purposesA recent National Academies study concluded that there are numerous critical unmet needs for transformative methods and tools to fill technology gaps for carbohydrate based applications in healthenergy and materials scienceOne of the most critical remaining hurdles has been accessibility to mammalian enzymes required for glycan synthesismodificationand catabolismglycoenzymesThese glycoenzymes are essential for synthesis and modification of glycanand glycoprotein related therapeutics and biologics in the pharmaceutical industrydevelopment of applications in biological and biomedical glycoscienceproduction of analytical standardsand advancing our understanding of fundamental biochemical processesAccess to this diverse set of enzymes will solve an unmet need for these tools in a global glycomics glycobiology market that is predicted to reach $billion byIn prior studiesthe Moremen lab at the University of Georgia developed strategies for recombinant production of all known human glycoenzymestarget enzymesby expression in mammalian cellsThe broad utility of these enzymes was demonstrated for numerous biomedical applications and NIH program staff strongly suggested the formation of a commercial entity for the production of these enzymatic reagentsA biotech start up companyGlyco Expression TechnologiesIncwas launched into enhance the productionvalidationand dissemination of these key reagents based on the proof of concept studies for mammalian expression developed at the University of GeorgiaThuswe propose PhaseSpecific Aims that includeAimenhanced production of challenging glycoenzymes using custom cell linesnew vector designsand co transfection strategiesAimmaximized recombinant human glycoenzyme expressionpurificationand processingandAimoptimized and validated enzyme activityspecificityand storage of recombinant enzymesThese aims will advance the goals of developing critical tools to overcome major roadblocks in mammalian glycobiology and fulfill critical unmet needs to provide technologies essential for carbohydrate based applicationsThese transformative reagents will be delivered in stable and wellcharacterized formats with appropriate documentation for enzyme specificity and will provide a framework for the developing biological and biomedical applications that expand our knowledge in glycochemistry and glycobiology and advance carbohydrate based therapeutics PROJECT NARRATIVE Availability of mammalian glycoenzymes presents a significant roadblock for development of applications in biochemical and biomedical glycoscienceHuman glycoenzyme expression in mammalian cells will be expanded and developed for the generation of a well characterizedcommercially available catalog of glycoenzymes as reagents for researchdiagnostic and therapeutic applications in glycobiology and glycochemistry