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ICS-3 Vortrag: Dr. Renko de Vries,
Wageningen University,
Laboratory of Physical Chemistry and Colloid Science

Towards protein-polymer based artifical viruses

04 Jun 2012 14:00
Seminarraum A1-A3, Building 04.6


The production of monodisperse designed polypetides (or "protein-polymers") in recombinant micro-organisms has been around for quite some time now, with most efforts being focussed on hydrogels for medical applications, and protein polymers for encapsulation and targeted delivery. We have recently started to develop protein polymers that coat single DNA molecules, taking inspiration from the structure and interactions of viral capsid proteins. In particular, we consider triblock designs consisting of a DNA binding domain (a short sequence of basic residues), a self-assembly domain (based on a "silk-like", beta-sheet forming sequence), and a domain for providing colloidal stability (with a sequence loosely based on that of collagen). Protein-polymers are produced through large-scale fermentation in the yeast Pichia Pastoris. Simple bulk precipitation steps on the culture medium are enough to obtain large amounts (gram scale) of relatively pure product. As we will show, the protein polymers indeed coat single DNA molecules. Polymer-DNA complexes are significantly thicker and and stiffer than bare DNA. The incorporation of only a few silk-like beta-strands as a self-assembly domain into the protein polymer designs, makes the coated DNA inaccessible to DNA degrading enzymes. Protein-polymer designs such as the ones we present here  may be useful as simple models for the co-assembly of viral capsid proteins with nucleic acids, as non-viral gene delivery vehicles, as well as in DNA nanotechnology for modifying DNA physical properties such as DNA thickness and stiffness.