Isoporous Silicon Nanomembranes for Purification of Therapeutic Viruses

Abstract Viruses engineered for gene therapy and the destruction of tumor cellsoncolytic virusesare a growing medical market$ B bywith profound implications for human healthTo comply with FDA regulationsmost drug products remove microbial contaminants with sterile filtration as a final stepIn the case of virusesthe broad pore sizes and high internal surface areas of commercial sterile filtration membranes result in massive product lossConsequentlyGMP paradigms for the production of medical grade virus must implement aseptic practices at every step of productionSiMPore uses silicon based manufacturing to create ultrathinnm thickmembranes with precision pore sizes and more thanorders of magnitude less internal surface area than conventional sterile filtersThis proposal investigates the hypothesis that these distinctive properties will enable sterile filtration of virus with less thanlossIn Aimwe will develop and characterize ultrathin membranes with a high density ofm slit poresThis pore size matches the average pore size of commercial sterile filtersbut with a dramatic reduction in thickness and internal surface areaFunctional characterization will include sievingburst pressuresand hydraulic permeability testingIn Aimwe will evaluate SiMPore membranes as sterile filters by comparing loss and capacity directly tocommercial sterile membrane filtersWith success in Phase ISiMPoreandapos s membranes will be scaled up from chip based to sheet based formats and used in diafiltration modules as final processing step in actual viral manufacturing processes during Phase II Narrative The manufacture of viruses for gene therapy or as anti cancer agents cannot use sterile filtration as a final production step because of massive titer losswith conventional polymer membranesSiMPore uses silicon manufacturing to produce ultrathin membranes with precise pore sizes that should enable the filtration of virus with minimal lossThis project will develop SiMPore membranes for the sterile filtration of virus and compare performance directly against three commercial membrane filters