Binding of external ligands onto an engineered virus capsid

The development of novel delivery systems for therapeutic substancesincludes targeting of the carriers to a specific site or tissuewithin the body of the recipient. This can be accomplished byappropriate receptor-binding domains and requires linking ofthese domains to the carrier. We have used recombinantly expressedpolyomavirus-like particles as a model system and inserted thesequence of a WW domain into different surface loops of theviral capsid protein VP1. In one variant, the WW domain maintainedits highly selective binding properties of proline-rich ligandsand showed an increased affinity but also an accelerated association/dissociationequilibrium compared to the isolated WW domain, thus allowinga short-term coupling of external ligands onto the surface ofthe virus-like particles.