# Modular Virus Capsid Coatings for Biocatalytic DNA Origami Nanoreactors

## TL;DR

Researchers created a modular nanoreactor by combining virus capsids with DNA origami to control enzyme activity and substrate access.

## Contribution

A modular system that combines virus capsid coatings with DNA origami to enable controlled enzyme loading and substrate flux.

## Key findings

- Virus capsid proteins were assembled on DNA origami nanoreactors to allow size-selective substrate uptake.
- The capsid coating protects the biocatalytic unit from degradation and allows surface functionalization for targeting.
- The platform is suitable for biomedical applications and studying capsid protein properties.

## Abstract

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.