Application

An engineered protein for targeting disease-associated N-glycans.

Key Benefits

• High affinity, pH insensitive, no cofactors required.
• Applications in anticancer and antiviral therapeutics and research.
• Can aid in manufacturing monoclonal antibodies with desired N-glycosylation properties.

Market Summary

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.

Technical Summary

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.

Development Stage

• This agent has been assessed for thermostability by differential scanning fluorimetry (DSF), binding affinity to high-mannose N-glycans by surface plasmon resonance (SPR), N-glycan specificity by liquid chromatography-mass spectrometry (LC-MS), and structural basis of N-glycan recognition by X-ray crystallography.
• Additional pre-clinical studies are in progress.