Efficient and scalable microfluidic gene delivery to hematopoietic stem cells to treat blood diseases

Abstract The two dominant methods for delivering genome modifying molecules to cells for cell therapies, viral transduction and electroporation transfection, have process and technical limitations that hamper the development of cutting-edge cell therapies accessible to all. While viral vectors result in a high cost of goods with significant regulatory and health risks associated with manufacturing, electroporation results in unhealthy cells with low viability and off-target phenotype changes. CellFE’s microfluidic VECT technology enables cell transfections with high transfection efficiency, low off-target changes to the cell, and with an expanded cell processing range. This project aims to demonstrate the first commercial cell transfection platform designed for scalable ex vivo genetic modification of CD34+ hematopoietic stem/progenitor cells (HSPC) to develop treatments of genetic and infectious diseases including beta thalassemia, sickle cell disease, hemophilia, and HIV. Scalability means that process parameters used in the research and development phase of cell engineering will immediately apply to clinical scale (300-fold increase in number of processed cells) by simply exchanging a chip. A simpler manufacturing scale-up means a faster path to clinical testing and will be a significant value proposition for the technology. To achieve these goals, CellFE will pursue the following aims: (1) determine the optimal design to scaleup device channels for high-throughput, (2) transfer device fabrication from PDMS to injection molded plastic, (3) demonstrate genetic modification of a therapeutic gene at bench-top at a clinical processing rate, and (4) develop alpha prototype systems for testing in the labs of our pharmaceutical partners to generate paid pilot studies. These are the key technical aims of the SBIR Phase II project and are also the main milestones CellFE needs to accomplish in order to execute its business plan of developing, marketing, and selling cell transfection platforms for cell therapy manufacturing with the prospect to de-risk manufacturing development and reduce cost of goods versus current delivery techniques.