Modular Virus Capsid Coatings for Biocatalytic DNA Origami Nanoreactors

Protein cages and custom DNA structures have emerged as self-assembling nanocompartments to sequester enzymes and mimic the compartmentalization of naturally occurring biocatalytic reactions. Protein cages excel in gating the interaction between enzyme and substrate, which can be affected by the physicochemical properties of protein units, whereas the high addressability of DNA origami allows stoichiometric control over the enzyme loading and precise positioning of enzymes. Nevertheless, both approaches would benefit from overcoming the challenges related to controlled enzyme loading and substrate flux, which could be resolved by combining the two nanomaterials. Here, we assemble virus capsid proteins on an enzyme-loaded DNA origami nanoreactor in a modular manner and demonstrate size-selective uptake of substrate molecules depending on the amount and type of capsid protein used for the encapsulation. The capsid cage also protects the biocatalytic unit from degradation, and further functionalization of the reactor surface with an antibody fragment allows targeting for delivery purposes. Thus, our approach provides an attractive platform not only for biomedical applications but also, because of its modularity, for rapid investigation of the physicochemical properties of capsid proteins.