I-Corps: High Efficiency Transduction to Improve Manufacture of Cell Therapeutics

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

The broader impact/commercial potential of this I-Corps project is to improve gene and cell therapies which hold potential to make life-altering improvements in healthcare for a broad spectrum of diseases, including cancers, blood disorders, and genetic diseases. If successful, this project can help to expand the population that has access to these treatments, both by reducing the cost of production and by enabling new therapies that are currently infeasible due to the low efficiency of existing cell engineering processes. The team will seek to learn new ideas and methodologies for engaging participants and stakeholders in the cell therapy community. This includes contract manufacturing organizations, clinicians/physicians, regulatory representatives, pharmaceutical companies, and patient advocates, among others. In addition to cell and gene therapies, the team will connect with researchers using gene modification in basic biology and drug discovery applications. If successful on all fronts, this project has potential to aid the discovery and delivery of many new therapies for untreatable diseases. This I-Corps project addresses an inefficiency in the cell engineering process. In cell therapies, patient cells are reprogrammed with a genetic sequence to alter the cell behavior. This can involve teaching immune cells to clear cancer, or reprogramming bone marrow cells to produce missing clotting factor proteins to cure congenital disease. Although these treatments have demonstrated tremendous potential, many of the treatments suffer from the low efficiency of gene transfer. In some cases, the low efficiency may prevent the treatment from being effective. The state of the art uses lentivirus to introduce genes into cells, typically using 20-50 viral particles per cell. However, it has been clearly shown that a great portion of the virus vector is wasted, due largely to mass transport limitations. This project proposes to provide a reagent to decrease the quantity of lentivirus used in cell transductions by 10-fold and improve transduction efficiency with minimal disruption of current transduction protocols. This process co-localizes cells with virus to reduce diffusion distances, while maintaining a mild, aqueous environment and retaining a large reservoir of cell culture nutrients. 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.