Engineering and functionalization of large circular tandem repeat protein nanoparticles

By C. Correnti, J. Hallinan, Lindsey Doyle, Raymond O. Ruff, Carla A. Jaeger-Ruckstuhl, Yuexin Xu, B. Shen, Amanda Qu, C. Polkinghorn, D. Friend and 5 more. 2020

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Protein engineering has enabled the design of molecular scaffolds that display a wide variety of sizes, shapes, symmetries and subunit compositions. Symmetric protein-based nanoparticles that display multiple protein domains can exhibit enhanced functional properties due to increased avidity and improved solution behavior and stability. Here we describe the creation and characterization of a computationally designed circular tandem repeat protein (cTRP) composed of 24 identical repeated motifs, which can display a variety of functional protein domains (cargo) at defined positions around its periphery. We demonstrate that cTRP nanoparticles can self-assemble from smaller individual subunits, can be produced from prokaryotic and human expression platforms, can employ a variety of cargo attachment strategies and can be used for applications (such as T-cell culture and expansion) requiring high-avidity molecular interactions on the cell surface. Circular nanoparticles self-assembled from designed tandem repeat proteins are functionalized by fusing different protein domains at defined positions and copy numbers. These constructs can activate T cells via high-avidity interactions on the cell surface.

Subfields: Ecology, Molecular Biology