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用于发现纳米抗体的噬菌体展示合成文库及筛选平台。

Phage-displayed synthetic library and screening platform for nanobody discovery.

作者信息

Xia Baolong, Kim Ah-Ram, Liu Feimei, Han Myeonghoon, Stoneburner Emily, Makdissi Stephanie, Di Cara Francesca, Mohr Stephanie E, Ring Aaron, Perrimon Norbert

机构信息

Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States.

Department of Immunobiology, Yale School of Medicine, Boston, United States.

出版信息

Elife. 2025 Aug 1;14:RP105887. doi: 10.7554/eLife.105887.

DOI:10.7554/eLife.105887
PMID:40748049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12316454/
Abstract

Nanobodies, single-domain antibodies derived from camelid heavy-chain antibodies, are known for their high affinity, stability, and small size, which make them useful in biological research and therapeutic applications. However, traditional nanobody generation methods rely on camelid immunization, which can be costly and time-consuming, restricting their practical feasibility. In this study, we present a phage-displayed synthetic library for nanobody discovery. To validate this approach, we screened nanobodies targeting various secreted proteins. The nanobodies identified were suitable for applications such as immunostaining and immunoblotting, supporting the phage-displayed synthetic library as a versatile platform for nanobody development. To address the challenge of limited accessibility to high-quality synthetic libraries, this library is openly available for non-profit use.

摘要

纳米抗体是源自骆驼科动物重链抗体的单域抗体,以其高亲和力、稳定性和小尺寸而闻名,这使其在生物学研究和治疗应用中很有用。然而,传统的纳米抗体生成方法依赖于骆驼科动物免疫,这可能成本高昂且耗时,限制了它们的实际可行性。在本研究中,我们提出了一个用于纳米抗体发现的噬菌体展示合成文库。为了验证这种方法,我们筛选了针对各种分泌蛋白的纳米抗体。鉴定出的纳米抗体适用于免疫染色和免疫印迹等应用,支持噬菌体展示合成文库作为纳米抗体开发的通用平台。为应对高质量合成文库获取有限的挑战,该文库可供非营利性公开使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/e1129ad78c0c/elife-105887-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/d0a17c9b3ed3/elife-105887-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/16c88898990d/elife-105887-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/9f2ba61c8c8e/elife-105887-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/e0b5356ec581/elife-105887-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/efb6c87feb14/elife-105887-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/c3e7a486e309/elife-105887-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/eac40707675e/elife-105887-fig2-figsupp5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/6da0d5afe5ae/elife-105887-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/e1129ad78c0c/elife-105887-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/d0a17c9b3ed3/elife-105887-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/16c88898990d/elife-105887-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/9f2ba61c8c8e/elife-105887-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/e0b5356ec581/elife-105887-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/efb6c87feb14/elife-105887-fig2-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/c3e7a486e309/elife-105887-fig2-figsupp4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/eac40707675e/elife-105887-fig2-figsupp5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/6da0d5afe5ae/elife-105887-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa24/12316454/e1129ad78c0c/elife-105887-fig4.jpg

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Breaking barriers in antibody discovery: harnessing divergent species for accessing difficult and conserved drug targets.打破抗体发现的障碍:利用多样化的物种来获得难以靶向和保守的药物靶点。
MAbs. 2023 Jan-Dec;15(1):2273018. doi: 10.1080/19420862.2023.2273018. Epub 2023 Dec 5.
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UCSF ChimeraX: Tools for structure building and analysis.UCSF ChimeraX:结构构建和分析工具。
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