I-Corps: Secreted nucleic acid based gene reporter

William Marsh Rice University, Houston TX

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is to greatly enhance the effectiveness of cell therapies for diseases such as cancer and cardiovascular degeneration that accounted for almost half of all US deaths in 2015. Cellular therapies involve implanting cells into a patient with the goal of treating disease, such as immune cells to target and kill cancer or insulin-secreting cells for the treatment of diabetes. A major challenge is to monitor the cells after their introduction, both for continued survival and for function. This I-Corp project would explore the commercialize potential of a technology that could be used in current cell therapies and during development of new ones. This technology could dramatically reduce the multibillion-dollar therapeutic development costs by providing crucial information regarding how therapeutic cells function in animals during laboratory tests, and could significantly improve bio-manufacturing efficiency, a category that accounts for more than 25% of the cost to produce cell therapies. This I-Corps project aims to develop a technology platform that would allow cells to report on their function by secreting a small RNA molecule (barcode) into the bloodstream. Depending on how it is introduced into the genome of the cell, this barcode could report on the continued persistence of the cells or on whether the cells are expressing a particular gene and therefore performing a specific function. Multiple barcodes could be combined to report on cellular persistence and several functions simultaneously. This technology will allow, for the first time, the monitoring of function of implanted cells inside animals. In the future, it may be possible to engineer cancer-fighting immune cells to express a barcode and implant the cells into mice bearing cancer. This barcode will report on the increase or decrease of the number of therapeutic cells. It may also be possible to engineer the cells to report each time a cancer cell is encountered by secreting a different barcode.