A Highly Versatile Platform for Multiplexed Cell Engineering for Cancer Immunotherapy and Stem Cell Therapy

Despite their unprecedented efficacy in the clinic, cell and gene therapies remain inaccessible to many patients due to their immense cost and complex manufacturing. Currently, delivery of cell modulating materials (e.g. CAR) to cell types of interest is done through viral, lipid, or electroporation technologies which are expensive, can only accommodate specific cargos or cells, and lack scalability - creating a bottleneck. Portal is developing a universal delivery platform that is compatible across cell and cargo types using mechanoporation. Portal's technology is based on the principle of rapid mechanical deformation of cells to generate transient disruptions of the lipid bilayer that facilitate delivery to the cytoplasm of cells. We have been able to implement Portal technology for use with several therapeutically valuable cargo molecules across multiple cell types, including various primary immune cells, such as T cells, B cells, NK, and monocytes. For example, we have shown multiplexed delivery of mRNA and CRISPR RNP to naive T cells efficiently engineering more than 85% of total viable cells with both GFP expression and deletion of B2M. In addition, we have demonstrated robust expression of mRNA-based CD19-CAR in primary T cells, while maintaining high viability and functionality. In addition to mRNA, we have successfully delivered circular RNA, siRNAs, and proteins to primary immune cells and hematopoietic stem cells. The use of this silicon membrane-based delivery system simplifies the delivery process and enables scalable integration of Portal technology with existing clinical manufacturing equipment. Using Portal's clinical scale integration module, we have the capacity to deliver cargo to more than 1 billion cells per minute. We show high viability and over 90% mRNA expression in activated T cells when integrated into standard GMP manufacturing equipment. Portal's approach is simple, economical, amenable to many cell and cargo types, and scales from research to clinical applications. Portal technology has the potential to alleviate major bottlenecks enabling broader accessibility of impactful cell therapies.

No relevant conflicts of interest to declare.