I-Corps: Translation potential of a microfluidic device to improve gene editing of therapeutic cells

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

The broader impact of this I-Corps project is the development of a biotechnology tool to increase gene editing efficiency and accelerate the development of cell therapies. Gene editing technology, a method for making specific changes to the DNA of a cell, is used to turn human cells into therapeutic cells. The method may be used as a potential treatment and cure for many diseases including cancer. Currently, however, this application is limited by the low efficiency of gene editing, which results in only a few percent of the cells being engineered successfully and becoming therapeutic cells. This low yield makes cell therapy one of the most expensive treatments and creates significant unmet patient demand. With increased gene editing efficiency, more therapeutic cells may be created, which may lower the manufacturing cost of therapeutic cells and help cell therapies treat more patients. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of a microfluidic device to increase gene editing efficiency. To achieve successful gene editing, materials used for gene editing need to be delivered into cells and have access to the target genes. However, many genes are densely packed and hidden within the chromatin, which makes them difficult to reach and leads to low editing efficiency. This technology tackles this issue through a mechanism called cell massage. Cells are gently squeezed through microchannels within the device, and the mechanical stimulation on the cell nucleus opens the chromatin structure temporarily. This opening allows the genes to be more accessible to gene editing materials. This solution has been shown to lead to a 10-fold increase in gene editing efficiency. The increased efficiency may lower the epigenetic barrier and make it easier for gene editing tools to reach and edit target genes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.