Glykoengineering

Glykoengineering, also spelled glycoengineering, is the deliberate modification of glycan structures attached to proteins or cells to achieve desired properties. It encompasses interventions in glycosylation pathways during production as well as post-production remodeling of glycans. The field intersects glycoscience, biotechnology, and medicinal chemistry and covers both N-linked and O-linked glycosylation as well as cell-surface glycans.

Methods include genetic and metabolic engineering of host cells (for example CHO cells, yeast, plants) to alter glycosyltransferases and glycosidases, as well as knockout or overexpression strategies. In vitro approaches use purified enzymes to remodel glycans (enzymatic glycan remodeling), chemoenzymatic synthesis, and semisynthetic strategies. Advances rely on CRISPR-based editing, cell-free systems, and comprehensive analytical tools such as mass spectrometry and HPLC to verify structures.

Applications include producing therapeutic proteins with defined glycoforms to improve safety, efficacy, or pharmacokinetics; for example afucosylation to enhance ADCC or increased sialylation for extended half-life. Glykoengineering also enables development of vaccines and diagnostic reagents with specific glycan epitopes and supports cell therapies with controlled surface glycosylation.

Challenges include intrinsic heterogeneity of glycosylation, the complexity of glycan structures, and regulatory requirements for manufacturing consistency and quality control. Ongoing work seeks robust, scalable processes and standardized analytics to enable reproducible glycoforms across production scales and platforms.