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Nat Nanotechnol. 2014 Sep;9(9):698-702. doi: 10.1038/nnano.2014.169. Epub 2014 Aug 24.

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

Author information

1
1] Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6703 HB Wageningen, The Netherlands [2] Dutch Polymer Institute, John F. Kennedylaan 2, 5612 AB Eindhoven, The Netherlands [3].
2
1] Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden University, PO Box 9504, 2300 RA Leiden, The Netherlands [2] Center for Soft Matter Research, Department of Physics, New York University, 4 Washington Place, New York, New York 10003, USA.
3
Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6703 HB Wageningen, The Netherlands.
4
Laboratory of Materials and Interface Chemistry &Soft Matter CryoTEM Research Unit, Department of Chemical Engineering and Chemistry, and Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands.
5
Utrecht University, Van't Hoff Laboratory for Physical and Colloid Chemistry, Debye Institute of Nanomaterials Science, PO Box 80.051, 3508 TB Utrecht, The Netherlands.
6
1] Department of Biochemistry, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands [2] Dutch Polymer Institute, John F. Kennedylaan 2, 5612 AB Eindhoven, The Netherlands.
7
Department of Biochemistry, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
8
Wageningen UR Food &Biobased Research, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands.
9
1] Theory of Polymers and Soft Matter, Department of Applied Physics, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands [2] Institute for Theoretical Physics, Utrecht University, Leuvenlaan 4, 3584 CE Utrecht, The Netherlands.
10
1] Laboratory of Physical Chemistry and Colloid Science, Wageningen University, Dreijenplein 6, 6703 HB Wageningen, The Netherlands [2] Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, PO Box 196, 9700 AD Groningen, The Netherlands.

Abstract

Viruses are among the simplest biological systems and are highly effective vehicles for the delivery of genetic material into susceptible host cells. 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 therapy and as scaffolds in material science. 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 only. However, incorporating this type of supramolecular cooperativity into artificial viruses remains challenging. 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 virus. We show that our virus-like particles protect DNA against enzymatic degradation and transfect cells with considerable efficiency, making them promising delivery vehicles.

PMID:
25150720
DOI:
10.1038/nnano.2014.169
[Indexed for MEDLINE]

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