Self-assembling protein cages: from coiled-coil module to machine learning-driven <i>de novo</i> design of next-generation biomaterials

The rational design of self-assembling protein nanocages holds great promise for synthetic biology, biotechnology and biomedical applications. Protein nanocages are well-defined nanoparticles with an inner cavity formed by self-assembly of repetitive protein building blocks. These cavities can be tailored to encapsulate and protect cargo molecules such as drugs, enzymes, or imaging agents. The ability to design <i>de novo</i> protein cages has recently been revolutionized by new concepts of modular protein design, computational design of interacting surfaces and machine learning-based generative protein design. Protein cages can be designed in diverse architectures and sizes, and their assembly and disassembly can be regulated by chemical, biological, and physical signals. Here, we focus on the review of engineering strategies for the designed protein cages based on coiled coils or other modular protein domains, their functionalization and opportunities of customized engineered protein cages.