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

Journal: Journal of nanobiotechnology
PMID:

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.

Authors

  • Jiwei Liu
    Department of Oncology, The First Hospital of Dalian Medical University (FHDMU), Dalian, China.
  • Lei Wu
    Advanced Photonics Center, Southeast University, Nanjing, 210096, China.
  • Anqi Xie
    Department of Thoracic Surgery, Wuxi People's Hospital, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Nanjing Medical University, Wuxi, 214023, China.
  • Weici Liu
    Department of Thoracic Surgery, Wuxi People's Hospital, Wuxi Medical Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Nanjing Medical University, Wuxi, 214023, China.
  • Zhao He
    Research Center of Digital Radiation Imaging and Biomedical imaging, Beijing University of Aeronautics and Astronautics, Beijing, China.
  • Yuan Wan
    Department of Radiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, PR China.
  • Wenjun Mao
    Department of Cardio-thoracic Surgery, Nanjing Medical University Affiliated Wuxi People's Hospital, Wuxi, Jiangsu, China; Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: maowenjun1@njmu.edu.cn.