Research ArticleDrug Delivery

An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics

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Science Translational Medicine  14 Oct 2020:
Vol. 12, Issue 565, eabb0580
DOI: 10.1126/scitranslmed.abb0580

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Altering albumin for drug delivery

Ideally, protein-based biologic drugs could be given transmucosally, rather than intravenously or subcutaneously, but the efficiency of transmucosal drug uptake is poor. Bern et al. designed an albumin protein with three amino acid substitutions, E505Q/T527M/K573P (QMP), improving binding to the neonatal Fc receptor expressed on mucosal epithelial cells. This prevented intracellular degradation and enhanced mucosal uptake of proteins fused to QMP upon intranasal delivery. Activated factor VII was fused to QMP, prolonging half-life without impeding factor VII function in a mouse model of hemophilia B. QMP may be a suitable carrier for biologic drugs but will require further testing in large-animal models.

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