Back to Search
Start Over
An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics
- Source :
- 12:eabb0580, Science Translational Medicine
- Publication Year :
- 2020
- Publisher :
- American Association for the Advancement of Science (AAAS), 2020.
-
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.
- Subjects :
- Genetically modified mouse
Recombinant Fusion Proteins
albumin, half-life, fcrn, fusion proteins, coagulation
Socio-culturale
Serum Albumin, Human
Receptors, Fc
Immunoglobulin G
law.invention
LS1_1
Neonatal Fc receptor
LS1_5
law
Albumins
transmucosal delivery
Human albumin
protein engineering
albumin fusion proteins
half-life prolongation
Transcellular
Biological Products
biology
Chemistry
Histocompatibility Antigens Class I
Albumin
General Medicine
Cell biology
Paracellular transport
biology.protein
Recombinant DNA
Nasal administration
Half-Life
Subjects
Details
- Language :
- English
- ISSN :
- 19466234
- Database :
- OpenAIRE
- Journal :
- 12:eabb0580, Science Translational Medicine
- Accession number :
- edsair.doi.dedup.....24e3afbab5d3fd5d83466671e027f7c1