Modular Nucleic Acid Scaffolds for Synthesizing Monodisperse and Sequence-Encoded Antibody Oligomers

Synthesizing protein oligomers that contain exact numbers of multiple different proteins in defined architectures is challenging. DNA-DNA interactions can be used to program protein assembly into oligomers; however, existing methods require changes to DNA design to achieve different numbers and oligomeric sequences of proteins. Herein, we develop a modular DNA scaffold that uses only six synthetic oligonucleotides to organize proteins into defined oligomers. As a proof-of-concept, model proteins (antibodies) are oligomerized into dimers and trimers, where antibody function is retained. Illustrating the modularity of this technique, dimer and trimer building blocks are then assembled into pentamers containing three different antibodies in an exact stoichiometry and oligomeric sequence. In sum, this report describes a generalizable method for organizing proteins into monodisperse, sequence-encoded oligomers using DNA. This advance will enable studies into how oligomeric protein sequences affect material properties in areas spanning pharmaceutical development, cascade catalysis, synthetic photosynthesis, and membrane transport.