Dr. Iris Seitz, Aalto University, Finland

Building functional virus-(un)like nanostructures using nucleic acid origami

Viruses are the most abundant and diverse biological entity across Earth’s ecosystem. Despite causing (devastating) diseases, viruses are known for their outstanding material and assembly properties. In particular, the virus capsid proteins – the proteins that form a protective ‘shell’ around the genome of a virus – are utilized for constructing precisely structured protein assemblies. However, the resulting virus-based assemblies are typically limited to a specific size, shape, and topology, which are largely determined by the virus strain. Gaining control over the assembly process to reprogram the morphology, regardless of the virus strain, would be attractive for the development of new drug delivery systems and vaccines.

In this talk, I will show how we exploit DNA origami for guiding the assembly of (capsid) proteins into user-defined sizes and shapes. The assembly can be pictured like wrapping a present – the proteins assemble on top of differently shaped DNA origami, and different proteins are like different wrapping paper, thereby assigning certain properties to the protein-DNA origami assemblies, resulting in protection, targeting and enhanced uptake into cells.

On top of serving as a platform for protein assembly, the DNA origami can be tweaked to perform application-relevant functions. Firstly, enzymes were placed on the DNA origami surface, resulting in biocatalytic systems. At the same time, the assembled protein shell was used to gate enzyme-substrate interactions. Secondly, the DNA origami was upgraded with messenger RNA (mRNA). To this end, I will discuss the design and fabrication of these mRNA-DNA origami and subsequent protein translation extracellularly and in vitro.

The presented approach demonstrates the applicability of origami to template highly ordered virus-mimetic structures and promotes the development of functional and responsive protein-DNA origami-based multipurpose systems.