Chia, S., Tay, S. J., Song, Z., Yang, Y., Walsh, I., & Pang, K. T. (2023). Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content. Biomedicine & Pharmacotherapy, 163, 114757. https://doi.org/10.1016/j.biopha.2023.114757
Abstract:
The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically modified by various means to enhance their circulatory half-life. One approach is to manipulate the N-glycan composition of these agents. Among the many glycan constituents, sialic acid (specifically, N-acetylneuraminic acid) plays a critical role in extending circulatory half-life by masking the terminal galactose that would otherwise be recognised by the hepatic asialoglycoprotein receptor (ASGPR), resulting in clearance of the biotherapeutic from the circulation. This review aims to provide an illustrative overview of various strategies to enhance the pharmacokinetic/pharmacodynamic properties of recombinant therapeutic proteins through manipulation of their sialic acid content.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research is supported by core funding from: A*STAR
Grant Reference no. : C222812028
This research is supported by core funding from: A*STAR
Grant Reference no. : C210112057
This research / project is supported by the A*STAR - Start Up Fund
Grant Reference no. : NA