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封闭蛋白结合单链可变片段和抗原结合片段抗体可预防丙型肝炎病毒感染。

Occludin-binding single-chain variable fragment and antigen-binding fragment antibodies prevent hepatitis C virus infection.

机构信息

Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjuku-ku, Japan.

Department of Pharmaceutical Sciences, Teikyo Heisei University, Nakano-ku, Japan.

出版信息

FEBS Lett. 2021 Jan;595(2):220-229. doi: 10.1002/1873-3468.13975. Epub 2020 Nov 7.

Abstract

Occludin (OCLN) is a tetraspan membrane component of epithelial tight junctions and a known receptor for hepatitis C virus (HCV). Previously, we established functional monoclonal antibodies (mAbs) that bind to each extracellular loop of OCLN and showed their ability to prevent in vitro and in vivo HCV infection. In this study, we converted these mAbs to corresponding monovalent antigen-binding fragments (Fabs) and single-chain variable fragment (scFv) antibodies. These Fab fragments and scFv antibodies demonstrate similar binding specificity and affinity to parental anti-OCLN mAbs. Moreover, Fab fragments and scFv antibodies inhibit in vitro HCV infection. The small functional monovalent OCLN-binding probes reported in our study have high potential as drug candidates and tools for biological and pharmaceutical studies of OCLN.

摘要

紧密连接相关蛋白 4(occludin,OCLN)是上皮细胞紧密连接的跨膜成分,也是丙型肝炎病毒(hepatitis C virus,HCV)的已知受体。先前,我们构建了功能型单克隆抗体(monoclonal antibody,mAb),其可结合 OCLN 的每个细胞外环,并证实其具有预防体外和体内 HCV 感染的能力。在本研究中,我们将这些 mAb 转化为相应的单价抗原结合片段(fragment antigen binding,Fab)和单链可变片段(single-chain variable fragment,scFv)抗体。这些 Fab 片段和 scFv 抗体与亲本抗-OCLN mAb 具有相似的结合特异性和亲和力。此外,Fab 片段和 scFv 抗体可抑制体外 HCV 感染。本研究报道的这些具有功能的小分子单价 OCLN 结合探针具有作为药物候选物和用于 OCLN 的生物学和药物研究工具的巨大潜力。

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