--- res: bibo_abstract: - Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Jungmin foaf_name: Lee, Jungmin foaf_surname: Lee - foaf_Person: foaf_givenName: Andyna foaf_name: Vernet, Andyna foaf_surname: Vernet - foaf_Person: foaf_givenName: Nathalie foaf_name: Gruber, Nathalie foaf_surname: Gruber foaf_workInfoHomepage: http://www.librecat.org/personId=2C9C8316-AA17-11E9-B5C2-8BC2E5697425 - foaf_Person: foaf_givenName: Kasia M. foaf_name: Kready, Kasia M. foaf_surname: Kready - foaf_Person: foaf_givenName: Devin R. foaf_name: Burrill, Devin R. foaf_surname: Burrill - foaf_Person: foaf_givenName: Jeffrey C. foaf_name: Way, Jeffrey C. foaf_surname: Way - foaf_Person: foaf_givenName: Pamela A. foaf_name: Silver, Pamela A. foaf_surname: Silver bibo_doi: 10.1093/protein/gzab025 bibo_volume: 34 dct_date: 2021^xs_gYear dct_identifier: - UT:000746596900001 dct_isPartOf: - http://id.crossref.org/issn/1741-0126 - http://id.crossref.org/issn/1741-0134 dct_language: eng dct_publisher: Oxford University Press@ dct_title: Rational engineering of an erythropoietin fusion protein to treat hypoxia@ fabio_hasPubmedId: '34725710' ...