UC San Diego

Glycosylation is crucial to many biological functions. Therefore, its control and monitoring are essential in many fields, from fundamental science to biotechnology and clinical diagnostics applications. For example, there is a pressing need for effective and affordable glycoprotein biopharmaceuticals to combat diseases that affect millions worldwide. For these, it is essential to control their glycan structures precisely, which can considerably impact their safety and efficacy. However, glycoengineering faces challenges due to the deficient understanding of glycosyltransferases—the enzymes that orchestrate glycan synthesis—and the subsequent effects of their manipulation on the host cell. Moreover, there is a need for high-throughput, cost-effective glycoprofiling techniques that can accurately characterize the resulting glycoforms of valuable biopharmaceuticals. In this dissertation, a comprehensive study will be conducted on the effects of glycoengineering on the cells used for biomanufacturing. This will be done by integrating glycoprofiles, bioprocessing phenotypes, and RNA-Seq data of glycoengineered CHO cells. Accelerating the characterization of their glycoprotein products will also be followed by an AI-based approach to assay N-glycan structures and their relative abundance using lectin-binding patterns. Finally, through the development of further computational modeling lectin binding kinetics and genomic methods, this method will be translated to a Next-generation sequencing platform. Thus, this dissertation will create a powerful new toolkit that will help accelerate cell line development for biomanufacturing.