dc.date.accessioned | 2021-01-23T19:27:29Z | |
dc.date.available | 2021-01-23T19:27:29Z | |
dc.date.created | 2020-11-02T12:45:03Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Bern, Malin C. Nilsen, Jeannette Ferrarese, Mattia Sand, Kine Marita Knudsen Tollefsrud Gjølberg, Torleif Lode, Heidrun Elisabeth Davidson, Robert J. Camire, Rodney M. Bækkevold, Espen Sønderaal Foss, Stian Grevys, Algirdas Dalhus, Bjørn Wilson, John Høydahl, Lene Christianson, Gregory J. Roopenian, Derry C. Schlothauer, Tilman Michaelsen, Terje Einar Moe, Morten Carsten Lombardi, Silvia Pinotti, Mirko Sandlie, Inger Branchini, Alessio Andersen, Jan Terje . An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Science Translational Medicine. 2020, 12:eabb0580(565), 1-13 | |
dc.identifier.uri | http://hdl.handle.net/10852/82549 | |
dc.description.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. | |
dc.language | EN | |
dc.publisher | American Association for the Advancement of Scienc | |
dc.title | An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics | |
dc.type | Journal article | |
dc.creator.author | Bern, Malin C. | |
dc.creator.author | Nilsen, Jeannette | |
dc.creator.author | Ferrarese, Mattia | |
dc.creator.author | Sand, Kine Marita Knudsen | |
dc.creator.author | Tollefsrud Gjølberg, Torleif | |
dc.creator.author | Lode, Heidrun Elisabeth | |
dc.creator.author | Davidson, Robert J. | |
dc.creator.author | Camire, Rodney M. | |
dc.creator.author | Bækkevold, Espen Sønderaal | |
dc.creator.author | Foss, Stian | |
dc.creator.author | Grevys, Algirdas | |
dc.creator.author | Dalhus, Bjørn | |
dc.creator.author | Wilson, John | |
dc.creator.author | Høydahl, Lene | |
dc.creator.author | Christianson, Gregory J. | |
dc.creator.author | Roopenian, Derry C. | |
dc.creator.author | Schlothauer, Tilman | |
dc.creator.author | Michaelsen, Terje Einar | |
dc.creator.author | Moe, Morten Carsten | |
dc.creator.author | Lombardi, Silvia | |
dc.creator.author | Pinotti, Mirko | |
dc.creator.author | Sandlie, Inger | |
dc.creator.author | Branchini, Alessio | |
dc.creator.author | Andersen, Jan Terje | |
cristin.unitcode | 185,53,18,15 | |
cristin.unitname | Avdeling for farmakologi | |
cristin.ispublished | true | |
cristin.fulltext | postprint | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1844105 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Science Translational Medicine&rft.volume=12:eabb0580&rft.spage=1&rft.date=2020 | |
dc.identifier.jtitle | Science Translational Medicine | |
dc.identifier.volume | 12 | |
dc.identifier.issue | 565 | |
dc.identifier.doi | https://doi.org/10.1126/scitranslmed.abb0580 | |
dc.identifier.urn | URN:NBN:no-85442 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1946-6234 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/82549/1/Postnr%2B1844105_Bern_Andersen_abb0580_manuscript_supl.pdf | |
dc.type.version | AcceptedVersion | |
cristin.articleid | eabb0580 | |
dc.relation.project | NFR/143822 | |
dc.relation.project | NFR/267606 | |
dc.relation.project | NFR/179573 | |
dc.relation.project | NFR/230526 | |
dc.relation.project | NFR/251037 | |