Design and self-assembly of simple coat proteins for artificial viruses

Hernandez Garcia, A.; Kraft, D.J.; Janssen, A.F.J.; Bomans, P.H.H.; Sommerdijk, N.A.J.M.; Thies-Weesie, D.M.E.; Favretto, M.E.; Brock, R.; Wolf, F.A. de; Werten, M.W.T.; Schoot, P. van der; Cohen Stuart, M.A.; Vries, R.J. de


Viruses are among the simplest biological systems and are highly effective vehicles for the delivery of genetic material into susceptible host cells1. Artificial viruses can be used as model systems for providing insights into natural viruses and can be considered a testing ground for developing artificial life. Moreover, they are used in biomedical and biotechnological applications, such as targeted delivery of nucleic acids for gene therapy1, 2 and as scaffolds in material science3, 4, 5. In a natural setting, survival of viruses requires that a significant fraction of the replicated genomes be completely protected by coat proteins. Complete protection of the genome is ensured by a highly cooperative supramolecular process between the coat proteins and the nucleic acids, which is based on reversible, weak and allosteric interactions only6, 7, 8, 9. However, incorporating this type of supramolecular cooperativity into artificial viruses remains challenging10, 11, 12, 13, 14, 15. Here, we report a rational design for a self-assembling minimal viral coat protein based on simple polypeptide domains. Our coat protein features precise control over the cooperativity of its self-assembly with single DNA molecules to finally form rod-shaped virus-like particles. We confirm the validity of our design principles by showing that the kinetics of self-assembly of our virus-like particles follows a previous model developed for tobacco mosaic virus9. We show that our virus-like particles protect DNA against enzymatic degradation and transfect cells with considerable efficiency, making them promising delivery vehicles.