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Abstract Nanobodies (Nbs), derived from the variable domains of camelid heavy‐chain‐only antibodies, have emerged as a transformative tools in modern biomedicine owning to their nanoscale size, exceptional stability, and unique capacity to recognize cryptic epitopes inaccessible to conventional antibodies. This review provides a comprehensive and up‐to‐date overview of the Nb field, spanning fundamental discovery to advanced translational and clinical applications. We first describe the structural and biochemical features that distinguish Nbs from classical immunoglobulins and underpin their favorable biophysical properties. We then systematically summarize current strategies for Nb discovery and production, including the construction of immune, naive, and synthetic/semi‐synthetic libraries, state‐of‐the‐art display and screening technologies, and diverse expression platforms. A major focus is devoted to Nb applications in diagnostics and therapeutics. In diagnostics, we highlight their growing roles in in vitro biosensing and in vivo molecular imaging. In therapeutics, we critically discuss recent advances in cancer immunotherapies, infectious diseases intervention, and emerging applications targeting neurological disorders. Finally, we review the current landscape of clinical translation and approved Nb‐based medicines, and discuss remaining challenges and future perspectives. Collectively, this review aims to provide a rigorous and integrative resource for understanding the evolution of Nbs from diverse discovery platforms to next‐generation biomedical solutions.
Ye et al. (Tue,) studied this question.