Protein drugs disappear quickly from the blood
Erythropoietin, better known as EPO, is a hormone that stimulates the production of red blood cells. EPO drugs are used to treat anaemia, for example in patients with chronic kidney disease and in cancer patients receiving chemotherapy.
The first EPO drugs have a plasma half-life of only 4–11 hours when given into a vein (intravenously), and patients may need injections up to several times a week. For people who need treatment over a long period or for life, repeated injections can be a burden in everyday life.
Newer variants last longer but still have to be injected. It is also difficult to get protein drugs absorbed across mucosal surfaces, for instance in the nose or lungs.
A better carrier
Albumin is the most abundant protein in the blood and has a plasma half-life of about three weeks in humans. This is because albumin binds to a receptor called FcRn, which rescues it from being broken down. The same receptor can also transport albumin across mucosal surfaces.
The Andersen group has previously developed an albumin variant, called QMP, that binds human FcRn far more strongly than normal albumin (Science Translational Medicine, 2020) (external link). In the new study, the researchers genetically fused EPO to this variant.
“Instead of only focusing on the therapeutic protein itself, we have engineered its carrier. By doing so, we can control how long the fusion protein stays in circulation and, at the same time, improve its ability to cross selective biological barriers. This study shows how an understanding of the fundamental biology that regulates albumin homeostasis can be used to design engineered albumin-fused biologics with tailored transport properties,” Andersen explains.
Lasting longer in the blood
The experiments were carried out in mice that expressing the human version of FcRn. Given intravenously, EPO fused to QMP albumin had a plasma half-life of 5.7 days, compared with 1.1 days for EPO fused to normal albumin, more than five times longer. The QMP version could be detected in the blood for up to 27 days, whereas the version with normal albumin could no longer be measured after 10 days. The half-life was about the same when the protein was given under the skin (subcutaneously).
The fusion protein bound the EPO receptor as well as the long-acting EPO drug darbepoetin alfa. After a single dose, both increased the number of red blood cells, but while the effect declined after one week in mice given darbepoetin alfa, levels stayed high for two weeks with the QMP version. After 24 days, these mice still had more red blood cells than those given darbepoetin alfa.
Absorbed through the nose
When the protein was given in the nose, five times as much of the QMP version reached the blood as the version with normal albumin. Compared with darbepoetin alfa given the same way, the QMP version produced a greater and more lasting increase in red blood cells.
“The combination of long circulatory half-life and improved ability to cross mucosal barriers is particularly exciting. Our results show that we can use QMP and its receptor, FcRn, as a transport system,” says Andersen.
A collaboration across countries
The study was carried out by researchers at the University of Oslo and Oslo University Hospital together with international partners, including The Jackson Laboratory in USA (external link) and Roche in Germany (external link).
The research was supported by, among others, the Research Council of Norway through its Centres of Excellence scheme and other grants, the South-Eastern Norway Regional Health Authority, and the Novo Nordisk Foundation through a Distinguished Innovator Grant.
The way ahead
The study is preclinical, and the results have so far been shown in mice. The researchers believe the principle could allow EPO to be given less often, and in some cases without a needle.
“Protein medicines are normally injected because they do not readily cross the body’s barriers. This could potentially contribute to protein-based medicines that can be given less frequently and perhaps, for some applications, without needles,” says Andersen.
Further reading
Anthi AK, Bejan D, Mester S, et al. A human erythropoietin-albumin fusion protein tailored for enhanced plasma half-life and delivery across mucosal surfaces. Nature Communications. 2026;17:10780. doi:10.1038/s41467-026-78243-z
Bern M, et al. An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Science Translational Medicine. 2020;12(565):eabb0580. doi:10.1126/scitranslmed.abb0580
Artificial intelligence has been used as a tool in the work on this article. The text has been edited and quality-checked by the author.