A Microscale Platform for Augmentation of Cell Transduction (MPACT) to Enhance Ex Vivo Gene Transfer

PROJECT SUMMARY ABSTRACT Recent advances in clinical gene therapy highlight the need for improved lentiviral vectorLVand adenoassociated viralAAVvector manufacture and utilization efficiencies for enhanced therapeutics outcomesExpression Therapeutics in collaboration with Emory University are developing a microfluidicFluidictechnology based solution that overcomes the mass transport and diffusion limitations of current transduction platforms to enhance ex vivo vector gene transfer kinetics and efficiencyThis novel ex vivo transduction platform is flexible in designscalableand compatible with standard cell culture transduction reagents and vector preparations as it mechanistically relies solely on physical principlesUsing hematopoietic cell linesprimary human T cellsand primary hematopoietic stem progenitor cellswe have demonstrated thatFluidic transduction occurs up tofold faster and requiresth of LV needed in conventional clinical transduction protocolsIn vivo application ofFluidics using hematopoietic stem progenitor cells of CBLJ hemophilia A mice transduced with factor VIII encoding LV and transplanted into hemophilic donors demonstrated that LV usage and transduction time is significantly reduced with our platformwithout loss of hematopoietic stem cell engraftment potentialThe milestones proposed for the current phase I SBIR application are todesign and test microfluidic devices scaled up to process andgttarget cell for genetically modified cell product manufacture validation at clinically relevant scalesvalidate these devices using clinically relevant primary human cell targetsCDcells and CDT cellsandexplore the opportunity for application of the microfluidic transduction devices to ex vivo AAV gene transferwhich is being pursued clinically for ex vivo gene editing and transient gene expression applications PROJECT NARRATIVE Gene therapy products are currently demonstrating tremendous potential in clinical trials for many genetic disorders and malignanciesbut commercialization progress is hampered by manufacturing limitations and costsThe objective of the current project is to commercialize a novel microfluidic transduction device that will dramatically improve gene therapy modalities by reducing costs and time required for the generation of genetically modified cell therapy productsIn the current phase I SBIR projectExpression Therapeutics will focus on continued development of our microfluidic transduction device to achieve proof of concept data at clinically relevant scales as well as demonstrate expanded utility of the device for ex vivo gene therapy and gene editing based application