An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics.
Document Type
Article
Publication Date
10-14-2020
Keywords
JMG
JAX Source
Sci Transl Med 2020 Oct 14; 12(565):eabb0580
Volume
12
Issue
565
ISSN
1946-6242
PMID
33055243
DOI
https://doi.org/10.1126/scitranslmed.abb0580
Abstract
Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.
Recommended Citation
Bern M,
Nilsen J,
Ferrarese M,
Sand K,
Gjølberg T,
Lode H,
Davidson R,
Camire R,
Bækkevold E,
Foss S,
Grevys A,
Dalhus B,
Wilson J,
Høydahl L,
Christianson GJ,
Roopenian DC,
Schlothauer T,
Michaelsen T,
Moe M,
Lombardi S,
Pinotti M,
Sandlie I,
Branchini A,
Andersen J.
An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Sci Transl Med 2020 Oct 14; 12(565):eabb0580