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通过嫁接功能性单互补决定区环实现抗体的胞质递送。

Cytoplasmic delivery of antibodies through grafting a functional single complementarity-determining region loop.

作者信息

Jeon Yerin, Choi Juho, Roh Youngin, Lee Eunbin, Villamante Luigie, Kwon Myung-Hee

机构信息

Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, South Korea.

Department of Microbiology, Ajou University School of Medicine, Suwon, South Korea.

出版信息

FEBS Lett. 2025 May;599(10):1442-1455. doi: 10.1002/1873-3468.70058. Epub 2025 May 1.

Abstract

The mouse 3D8 anti-DNA antibody can enter cells and localize in the cytoplasm, primarily facilitated by the complementarity-determining region 1 of the variable light chain (CDR L1) domain. In this study, we grafted the CDR L1 loop from 3D8 onto non-cell-penetrating IgG antibodies to investigate whether these IgGs could acquire cytoplasmic localization ability while retaining antigen-binding activity. One of three IgGs was successfully delivered into the cytoplasm while maintaining antigen-binding activity. In silico protein modeling suggests that this capability is linked to structural similarity between CDR L1 in the grafted Ab and that in 3D8. This study proposes a strategy to confer cell-penetrating capability by incorporating a specific CDR loop into an antibody backbone while retaining affinity.

摘要

小鼠3D8抗DNA抗体能够进入细胞并定位于细胞质中,这主要是由可变轻链互补决定区1(CDR L1)结构域促成的。在本研究中,我们将3D8的CDR L1环移植到非细胞穿透性IgG抗体上,以研究这些IgG抗体在保留抗原结合活性的同时是否能够获得细胞质定位能力。三种IgG抗体中的一种成功地被递送至细胞质中,同时保持了抗原结合活性。计算机蛋白质建模表明,这种能力与移植抗体中的CDR L1和3D8中的CDR L1之间的结构相似性有关。本研究提出了一种策略,即通过将特定的CDR环整合到抗体骨架中同时保留亲和力来赋予细胞穿透能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12104855/8c70930a7ad4/FEB2-599-1442-g002.jpg

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