(331c) Novel Multimodal Membranes for AAV Full and Empty Capsid Separations

Viral vectors such as adeno-associated virus (AAV) particles are efficient gene delivery carriers. Unlike protein-based therapeutics, the development of purification platforms for viral vectors is far less ma­ture. In addition, the size, sensitivity and complexity of virus particles leads to additional challenges. Here AAV particles will be used as a model system to develop membrane-based purification processes for viral vectors. Some of these recombinant AAV particles contain no genomic materials resulting from the viral packaging processes. In fact, the ratio of empty to full capsids can be as high as 10:1. While these empty capsids are naturally occurring contaminants, their presence potentially reduces the effectiveness of the therapy by competing for cell-mediated processes. Current purification methods involve complex operations to remove empty capsids. Here multi-modal anion exchange membranes have been synthesized by grafting and multimodal ligands on commercially available regenerated cellulose membranes varying both the ligand chain length and chain density. At optimal grafting conditions, better resolution separation of full and empty AAV particles has been achieved with the fabricated multimodal membranes compared to commercially available membranes.