Oncologists are increasingly interested in harnessing the power of their patients' immune systems to aide in the ongoing battle against cancer. One example, adoptive cellular therapies, utilizes types of white blood cells known as T-cells that have been genetically engineered to recognize and recruit other cells of the immune system to attack malignant cells. These approaches have shown promise in pediatric patients with difficult to treat leukemias, but are limited to specialized academic centers in part by how efficiently (and quickly) they can be manufactured as well as by technical limitations in the strategies commonly used to deliver biomolecules for gene modification.
To address these challenges, this proposal focuses on developing and applying microfluidic technologies that enable delivery of gene-editing agents into cells rapidly via temporary pores that form at cellular membranes as cells are squeezed through narrow channels. This strategy is gentler and less toxic than competing approaches which require the use of external electric fields. To avoid clogging of the device we propose to line the microchannels with bio-inspired surface chemistries that prevent cells from becoming stuck via a "slip and slide" effect. The proposed platform will be used to demonstrate rapid and efficient gene-editing of T-cells at scales compatible with mass production to overcome obstacles in the clinical translation and deployment of cellular immunotherapies.