Viral vector gene delivery is a promising technique for the therapeutic administration of proteins to damaged tissue in order to improve regeneration outcomes in a variety of disease settings including brain and spinal cord injury as well as autoimmune diseases. Though promising results have been demonstrated, limitations of viral vectors, including spread of virus to distant sites, neutralisation by the host immune system and low transduction efficiencies have stimulated the investigation of biomaterials as gene delivery vehicles for improved protein expression at an injury site. Here, we show how N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptide (SAP) hydrogels, designed for tissue specific central nervous system (CNS) applications via incorporation of the laminin peptide sequence, isoleucine-lysine-valine-alanine-valine (IKVAV), are effective as biocompatible, localised viral vector gene delivery vehicles in vivo. Through the addition of a C-terminal lysine (K) residue, we show that increased electrostatic interactions, provided by the additional amine side-chain, allows the effective immobilisation of lentiviral vector particles, thereby constraining their activity exclusively to the site of injection and enabling focal gene delivery in vivo in a tissue specific manner. When the C-terminal lysine was absent there was no difference between the number of transfected cells, the volume of tissue transfected or the transfection efficiency with and without the Fmoc-SAP. Importantly, immobilisation of the virus only effected transfection cell number and volume with no impact observed on transfection efficiency. This hydrogel allows the sustained and targeted delivery of growth factors post injury. We have established Fmoc-SAPs as a versatile platform for enhanced biomaterial design for a range of tissue engineering applications.
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