An engineered protein for targeting disease-associated N-glycans.
Glycosylation involves post-translation addition of specific glycans to proteins or lipids. Abnormal glycosylation is an emerging biomarker of diverse cancer types (colorectal, pancreatic, ovarian, breast, prostate, and skin) and virus strains (including HIV, HSV-1, HCV, influenza, Ebola, and SARS-CoV-2). Glycosylation can also impact stability, structure, and function of monoclonal antibodies (mABs). The market for targeting glycosylation—including glycomics research, glycosylation analysis services, and glycoengineered therapeutics—is growing rapidly. Key drivers of this growth are increasing research investments by biopharmaceutical companies into glycosylation analysis and glycoengineering, rising prevalence of diseases where glycosylation plays a key role, and expanding potential applications in vaccines, antibody production, and precision medicine.
To selectively target disease-related glycosylation characterized by high-mannose N-glycans, Emory researchers modified a glycan degrader enzyme prominent in the human gut microbe to engineer an enzyme that is highly thermostable across a wide pH range and binds tightly to high-mannose N-glycans. This technology has three potential use cases: (1) When fused to therapeutic agents such as CAR-T cells, this technology has the potential to selectively target disease-related glycoproteins on malignant tumor and supporting stromal cells. (2) When fused to Fc, it may confer potential antiviral properties by targeting viral glycoproteins. (3) It can enable affinity-based purification of monoclonal antibodies during manufacturing, separating high-mannose from complex-type N-glycosylated antibodies.