Advances in designed bionanomolecular assemblies for biotechnological and biomedical applications

Recent advances in protein engineering have revolutionized the design of bionanomolecular assemblies for functional therapeutic and biotechnological applications. This review highlights the progress in creating complex protein architectures, encompassing both finite and extended assemblies. AI tools, including AlphaFold, RFDiffusion, and ProteinMPNN, have significantly enhanced the scalability and success of de novo designs. Finite assemblies, like nanocages and coiled-coil-based structures, enable precise molecular encapsulation or functional protein domain presentation. Extended assemblies, including filaments and 2D/3D lattices, offer unparalleled structural versatility for applications such as vaccine development, responsive biomaterials, and engineered cellular scaffolds. The convergence of artificial intelligence-driven design and experimental validation promises strong acceleration of the development of tailored protein assemblies, offering new opportunities in synthetic biology, materials science, biotechnology, and biomedicine.