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The neonatal Fc receptor (FcRn) regulates the persistence of immunoglobulin G (IgG) by the FcRn\u2010mediated recycling pathway, which salvages IgG from lysosomal degradation within cells. In this study, Fc\u2010engineering of antirabies virus therapeutic mAb SO57 with the endoplasmic reticulum (ER)\u2010retention peptide signal (Lys\u2010Asp\u2010Glu\u2010Leu; KDEL) (mAb<jats:sup>p<\/jats:sup>K SO57) in plant cell was conducted to enhance its binding activity to human neonatal Fc receptor (hFcRn), consequently improve its serum half\u2010life. Enzyme\u2010linked immunosorbent assay (ELISA) and Surface plasmon resonance assay showed altered binding affinity of the Fc region of three different mAb<jats:sup>p<\/jats:sup>K SO57 variants [M252Y\/S254T\/T256E (MST), M428L\/N434S (MN), H433K\/N434F (HN)] to hFcRn compared to wild type (WT) of mAb<jats:sup>p<\/jats:sup>K SO57. Molecular modeling data visualized the structural alterations in these mAb<jats:sup>p<\/jats:sup>K SO57. All of the mAb<jats:sup>p<\/jats:sup>K SO57 variants had HM type glycan structures similar to the WT mAb<jats:sup>p<\/jats:sup>K SO57. In addition, the neutralizing activity of the three variants against the rabies virus CVS\u201011 was effective as the WT mAb<jats:sup>p<\/jats:sup>K SO57. These results indicate that the binding affinity of mAb<jats:sup>p<\/jats:sup>K SO57 variants to hFcRn can be modified without alteration of <jats:italic>N\u2010<\/jats:italic>glycan structure and neutralization activity. Taken together, this study suggests that Fc\u2010engineering of antirabies virus mAb can be applied to enhance the efficacy of therapeutic mAbs in plant expression systems.<\/jats:p>","DOI":"10.1002\/biot.202300552","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:35:32Z","timestamp":1711413332000},"source":"Crossref","is-referenced-by-count":7,"title":["Fc engineered anti\u2010virus therapeutic human IgG<sub>1<\/sub> expressed in plants with altered binding to the neonatal Fc receptor"],"prefix":"10.1002","volume":"19","author":[{"given":"Sol\u2010Ah","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonji","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chung\u2010Ang University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjoo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Joo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yerin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiquan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Joo","family":"An","sequence":"additional","affiliation":[{"name":"Graduate School of Analytical Science and Technology Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Jin","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Applied Experimental Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hinterdorfer","sequence":"additional","affiliation":[{"name":"Department of Applied Experimental Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhye","family":"Kim","sequence":"additional","affiliation":[{"name":"Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Choi","sequence":"additional","affiliation":[{"name":"Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4964-0845","authenticated-orcid":false,"given":"Kisung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Medicine BioSystems Design Lab College of Medicine Chung\u2010Ang University  Dongjak\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.28744"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2022.55.3.090"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd984"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903296"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI106279"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.739"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810796106"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107116"},{"key":"e_1_2_9_10_1","first-page":"682","article-title":"Unraveling the interaction between FcRn and albumin: Opportunities for design of albumin\u2010based therapeutics","volume":"5","author":"Sand K. 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