A human erythropoietin-albumin fusion protein tailored for enhanced plasma half-life and delivery across mucosal surfaces
Abstract
Erythropoietin (EPO) products stimulate production of erythrocytes in patients with anemia. The drugs are delivered intravenously or subcutaneously up to several times per week due to short plasma half-life. Improving the pharmacokinetic properties of EPO will allow less frequent administration, and thus impact therapeutic utility and patient compliance. In this study, we took advantage of an albumin variant (QMP) engineered for improved engagement of FcRn, a key regulator of the plasma half-life of albumin. After genetic coupling of EPO to QMP, the fusion protein shows favorable neonatal Fc receptor (FcRn) binding, and 5.2-fold prolonged plasma half-life in human FcRn expressing mice upon intravenous administration, when comparing with EPO fused to WT albumin, with a similar half-life obtained following subcutaneous administration. Importantly, both fusions bind the EPO receptor with binding kinetics equal to that of the product darbepoetin alfa. After intravenous administration, mice receiving darbepoetin alfa experiences a faster drop in EPO levels compared to those given EPO-QMP, and moreover, we measure a prolonged increase in erythrocytes with EPO-QMP. Furthermore, intranasal administration results in 5-fold higher circulating amounts of EPO-QMP and a prolonged increase in erythrocytes compared to darbepoetin alfa. Thus, long-acting EPO-QMP could be an attractive design to explore for both invasive and non-invasive delivery to patients with anemia.
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BibTeX
@article{anthi2026human,
title = {{A human erythropoietin-albumin fusion protein tailored for enhanced plasma half-life and delivery across mucosal surfaces}},
author = {Aina Karen Anthi and Daniela Bejan and Simone Mester and Nijaguna Bethur and Elena Gonzalo-Gil and Sopisa Benjakul and Kristin Hovden Aaen and Tilman Schlothauer and Inger Sandlie and Jan Terje Andersen},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78243-z},
url = {https://www.nature.com/articles/s41467-026-78243-z},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A human erythropoietin-albumin fusion protein tailored for enhanced plasma half-life and delivery across mucosal surfaces
AU - Aina Karen Anthi
AU - Daniela Bejan
AU - Simone Mester
AU - Nijaguna Bethur
AU - Elena Gonzalo-Gil
AU - Sopisa Benjakul
AU - Kristin Hovden Aaen
AU - Tilman Schlothauer
AU - Inger Sandlie
AU - Jan Terje Andersen
PY - 2026
DA - 2026/10/28
JO - Nature Communications
DO - 10.1038/s41467-026-78243-z
UR - https://www.nature.com/articles/s41467-026-78243-z
AB - Erythropoietin (EPO) products stimulate production of erythrocytes in patients with anemia. The drugs are delivered intravenously or subcutaneously up to several times per week due to short plasma half-life. Improving the pharmacokinetic properties of EPO will allow less frequent administration, and thus impact therapeutic utility and patient compliance. In this study, we took advantage of an albumin variant (QMP) engineered for improved engagement of FcRn, a key regulator of the plasma half-life of albumin. After genetic coupling of EPO to QMP, the fusion protein shows favorable neonatal Fc receptor (FcRn) binding, and 5.2-fold prolonged plasma half-life in human FcRn expressing mice upon intravenous administration, when comparing with EPO fused to WT albumin, with a similar half-life obtained following subcutaneous administration. Importantly, both fusions bind the EPO receptor with binding kinetics equal to that of the product darbepoetin alfa. After intravenous administration, mice receiving darbepoetin alfa experiences a faster drop in EPO levels compared to those given EPO-QMP, and moreover, we measure a prolonged increase in erythrocytes with EPO-QMP. Furthermore, intranasal administration results in 5-fold higher circulating amounts of EPO-QMP and a prolonged increase in erythrocytes compared to darbepoetin alfa. Thus, long-acting EPO-QMP could be an attractive design to explore for both invasive and non-invasive delivery to patients with anemia.
SN - 2041-1723
ER -