Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity
DC Field | Value | Language |
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dc.contributor.author | Lee, Jong Youl | - |
dc.contributor.author | Park, Taehoon | - |
dc.contributor.author | Hong, Eunmi | - |
dc.contributor.author | Amatya, Reeju | - |
dc.contributor.author | Park, Kyung-Ah | - |
dc.contributor.author | Park, Young-Hoon | - |
dc.contributor.author | Min, Kyoung Ah | - |
dc.contributor.author | Jin, Minki | - |
dc.contributor.author | Lee, Sumi | - |
dc.contributor.author | Hwang, Seungmi | - |
dc.contributor.author | Roh, Gu Seob | - |
dc.contributor.author | Shin, Meong Cheol | - |
dc.date.accessioned | 2022-12-26T12:17:52Z | - |
dc.date.available | 2022-12-26T12:17:52Z | - |
dc.date.created | 2022-12-12 | - |
dc.date.issued | 2020-10 | - |
dc.identifier.issn | 0142-9612 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gnu/handle/sw.gnu/6101 | - |
dc.description.abstract | A common bottleneck challenge for many therapeutic proteins lies in their short plasma half-lives, which often makes the treatment far less compliant or even disables achieving sufficient therapeutic efficacy. To address this problem, we introduce a novel drug delivery strategy based on the genetic fusion of an albumin binding domain (ABD) and an anti-neonatal Fc receptor (FcRn) affibody (AFF) to therapeutic proteins. This ABD-AFF fusion strategy can provide a synergistic effect on extending the plasma residence time by, on one hand, preventing the rapid glomerular filtration via ABD-mediated albumin binding and, on the other hand, increasing the efficiency of FcRn-mediated recycling by AFF-mediated high-affinity binding to the FcRn. In this research, we explored the feasibility of applying the ABD-AFF fusion strategy to exendin-4 (EX), a clinically available anti-diabetic peptide possessing a short plasma half-life. The EX-ABD-AFF produced from the E. coli displayed a remarkably (241-fold) longer plasma half-life than the SUMO tagged-EX (SUMO-EX) (0.7 h) in mice. Furthermore, in high-fat diet (HFD)-fed obese mice model, the EX-ABD-AFF could provide significant hypoglycemic effects for over 12 days, accompanied by a reduction of body weight. In the long-term study, the EX-ABD-AFF could significantly reverse the obesity-related metabolic complications (hyperglycemia, hyperlipidemia, and hepatic steatosis) and, more-over, improve cognitive deficits. Overall, this study demonstrated that the ABD-AFF fusion could be an effective strategy to greatly increase the plasma half-lives of therapeutic proteins and thus markedly improve their druggability. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCI LTD | - |
dc.subject | HALF-LIFE | - |
dc.subject | AFFIBODY MOLECULE | - |
dc.subject | PEPTIDE-1 GLP-1 | - |
dc.subject | EXENATIDE | - |
dc.subject | RECEPTOR | - |
dc.subject | ALBUMIN | - |
dc.subject | BINDING | - |
dc.subject | FUSION | - |
dc.subject | BRAIN | - |
dc.subject | PHARMACOKINETICS | - |
dc.title | Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Roh, Gu Seob | - |
dc.contributor.affiliatedAuthor | Shin, Meong Cheol | - |
dc.identifier.doi | 10.1016/j.biomaterials.2020.120250 | - |
dc.identifier.scopusid | 2-s2.0-85088655802 | - |
dc.identifier.wosid | 000563958400002 | - |
dc.identifier.bibliographicCitation | BIOMATERIALS, v.257 | - |
dc.relation.isPartOf | BIOMATERIALS | - |
dc.citation.title | BIOMATERIALS | - |
dc.citation.volume | 257 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Engineering | - |
dc.relation.journalResearchArea | Materials Science | - |
dc.relation.journalWebOfScienceCategory | Engineering, Biomedical | - |
dc.relation.journalWebOfScienceCategory | Materials Science, Biomaterials | - |
dc.subject.keywordPlus | HALF-LIFE | - |
dc.subject.keywordPlus | AFFIBODY MOLECULE | - |
dc.subject.keywordPlus | PEPTIDE-1 GLP-1 | - |
dc.subject.keywordPlus | EXENATIDE | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | ALBUMIN | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | FUSION | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordAuthor | Exendin-4 | - |
dc.subject.keywordAuthor | Albumin binding domain | - |
dc.subject.keywordAuthor | FcRn | - |
dc.subject.keywordAuthor | Affibody | - |
dc.subject.keywordAuthor | GLP-1R | - |
dc.subject.keywordAuthor | Obesity | - |
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