DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Tae Yoon | ko |
dc.contributor.author | Park, Jin Ho | ko |
dc.contributor.author | Shim, Ha Eun | ko |
dc.contributor.author | Choi, Dae Seong | ko |
dc.contributor.author | Lee, Dong-Eun | ko |
dc.contributor.author | Song, Ji-Joon | ko |
dc.contributor.author | Kim, Hak-Sung | ko |
dc.date.accessioned | 2019-12-23T07:20:10Z | - |
dc.date.available | 2019-12-23T07:20:10Z | - |
dc.date.created | 2019-12-23 | - |
dc.date.issued | 2019-12 | - |
dc.identifier.citation | JOURNAL OF CONTROLLED RELEASE, v.315, pp.31 - 39 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | http://hdl.handle.net/10203/270278 | - |
dc.description.abstract | Many small-sized proteins and peptides, such as cytokines and hormones, are clinically used for the treatment of a variety of diseases. However, their short half-life in blood owing to fast renal clearance usually results in a low therapeutic efficacy and frequent dosing. Here we present the development of a human serum albumin (HSA)specific protein binder with a binding affinity of 4.3 nM through a phage display selection and modular evolution approach to extend the blood half-life of a small-sized therapeutic protein. As a proof-of-concept, the protein binder composed of LRR (Leucine-rich repeat) modules was genetically fused to the N-terminus of Glucagon-like Peptide-1 (GLP-1). The fused GLP-1 was shown to have a significantly improved pharmacokinetic property: The terminal half-life of the fused GLP-1 increased to approximately 10 h, and the area under the curve was 5-times higher than that of the control. The utility and potential of our approach was demonstrated by the efficient control of the blood glucose level in type-2 diabetes mouse models using the HSA-specific protein binder-fused GLP-1 over a prolonged time period. The present approach can be effectively used in enhancing the efficacy of small-sized therapeutic proteins and peptides through an enhanced blood circulation time. | - |
dc.language | English | - |
dc.publisher | ELSEVIER | - |
dc.title | Prolonged half-life of small-sized therapeutic protein using serum albumin-specific protein binder | - |
dc.type | Article | - |
dc.identifier.wosid | 000500710700003 | - |
dc.identifier.scopusid | 2-s2.0-85074140532 | - |
dc.type.rims | ART | - |
dc.citation.volume | 315 | - |
dc.citation.beginningpage | 31 | - |
dc.citation.endingpage | 39 | - |
dc.citation.publicationname | JOURNAL OF CONTROLLED RELEASE | - |
dc.identifier.doi | 10.1016/j.jconrel.2019.09.017 | - |
dc.contributor.localauthor | Song, Ji-Joon | - |
dc.contributor.localauthor | Kim, Hak-Sung | - |
dc.contributor.nonIdAuthor | Park, Jin Ho | - |
dc.contributor.nonIdAuthor | Shim, Ha Eun | - |
dc.contributor.nonIdAuthor | Choi, Dae Seong | - |
dc.contributor.nonIdAuthor | Lee, Dong-Eun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Half-life | - |
dc.subject.keywordAuthor | Therapeutic protein | - |
dc.subject.keywordAuthor | Human serum albumin | - |
dc.subject.keywordAuthor | LRR protein | - |
dc.subject.keywordAuthor | Genetic fusion | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | PHARMACOKINETIC PROPERTIES | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | GLP-1 | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | STRATEGIES | - |
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