Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization

Abstract Nanobodies (Nbs), miniature antibodies consisting solely of the variable region of heavy chains, exhibit unique properties such as small size, high stability, and strong specificity, making them highly promising for disease diagnosis and treatment. The engineering production of Nbs has evol...

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Main Authors: Jiwei Liu, Lei Wu, Anqi Xie, Weici Liu, Zhao He, Yuan Wan, Wenjun Mao
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03169-5
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author Jiwei Liu
Lei Wu
Anqi Xie
Weici Liu
Zhao He
Yuan Wan
Wenjun Mao
author_facet Jiwei Liu
Lei Wu
Anqi Xie
Weici Liu
Zhao He
Yuan Wan
Wenjun Mao
author_sort Jiwei Liu
collection DOAJ
description Abstract Nanobodies (Nbs), miniature antibodies consisting solely of the variable region of heavy chains, exhibit unique properties such as small size, high stability, and strong specificity, making them highly promising for disease diagnosis and treatment. The engineering production of Nbs has evolved into a mature process, involving library construction, screening, and expression purification. Different library types, including immune, naïve, and synthetic/semi-synthetic libraries, offer diverse options for various applications, while display platforms like phage display, cell surface display, and non-surface display provide efficient screening of target Nbs. Recent advancements in artificial intelligence (AI) have opened new avenues in Nb engineering. AI’s exceptional performance in protein structure prediction and molecular interaction simulation has introduced novel perspectives and tools for Nb design and optimization. Integrating AI with traditional experimental methods is anticipated to enhance the efficiency and precision of Nb development, expediting the transition from basic research to clinical applications. This review comprehensively examines the latest progress in Nb engineering, emphasizing library construction strategies, display platform technologies, and AI applications. It evaluates the strengths and weaknesses of various libraries and display platforms and explores the potential and challenges of AI in predicting Nb structure, antigen-antibody interactions, and optimizing physicochemical properties. Graphical abstract
format Article
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institution Kabale University
issn 1477-3155
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj-art-b24c318cb7424e0c8a6e0499463a915c2025-02-09T12:53:09ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123112710.1186/s12951-025-03169-5Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimizationJiwei Liu0Lei Wu1Anqi Xie2Weici Liu3Zhao He4Yuan Wan5Wenjun Mao6Department of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityDepartment of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityThe Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton UniversityDepartment of Thoracic Surgery, Wuxi People’s Hospital, Wuxi Medical Center, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Nanjing Medical UniversityAbstract Nanobodies (Nbs), miniature antibodies consisting solely of the variable region of heavy chains, exhibit unique properties such as small size, high stability, and strong specificity, making them highly promising for disease diagnosis and treatment. The engineering production of Nbs has evolved into a mature process, involving library construction, screening, and expression purification. Different library types, including immune, naïve, and synthetic/semi-synthetic libraries, offer diverse options for various applications, while display platforms like phage display, cell surface display, and non-surface display provide efficient screening of target Nbs. Recent advancements in artificial intelligence (AI) have opened new avenues in Nb engineering. AI’s exceptional performance in protein structure prediction and molecular interaction simulation has introduced novel perspectives and tools for Nb design and optimization. Integrating AI with traditional experimental methods is anticipated to enhance the efficiency and precision of Nb development, expediting the transition from basic research to clinical applications. This review comprehensively examines the latest progress in Nb engineering, emphasizing library construction strategies, display platform technologies, and AI applications. It evaluates the strengths and weaknesses of various libraries and display platforms and explores the potential and challenges of AI in predicting Nb structure, antigen-antibody interactions, and optimizing physicochemical properties. Graphical abstracthttps://doi.org/10.1186/s12951-025-03169-5Nanobody engineeringLibrary constructionScreening platformsArtificial intelligenceDesign optimization
spellingShingle Jiwei Liu
Lei Wu
Anqi Xie
Weici Liu
Zhao He
Yuan Wan
Wenjun Mao
Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
Journal of Nanobiotechnology
Nanobody engineering
Library construction
Screening platforms
Artificial intelligence
Design optimization
title Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
title_full Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
title_fullStr Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
title_full_unstemmed Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
title_short Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization
title_sort unveiling the new chapter in nanobody engineering advances in traditional construction and ai driven optimization
topic Nanobody engineering
Library construction
Screening platforms
Artificial intelligence
Design optimization
url https://doi.org/10.1186/s12951-025-03169-5
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