Safe cell and gene therapy combination: are we there yet in arthritis?

Abstract

Pluripotent stem cells have accelerated the development of new avenues for targeting degenerative diseases and cancer, using cell-based therapies. Although these therapies are promising, concerns regarding cell-safety have hampered their implementation. Here, we introduce a concept and show the associated genome engineering strategy that addresses this safety issue; providing a solution for prospective cell therapies. Using a genome-engineered cell suicide switch that eliminates potential cancerous cells, we measured the mutation rate of this switch and mathematically defined the safety level of future therapies. Our approach to assess and quantify safety will be critical to the informed decisions made by regulators, doctors, and patients that will advance modern medicine. Furthermore, using a proof-of-principle experiment, we demonstrate that cells can also be used as a vehicle to produce biologics at a disease site. We engineered a local-acting TNFα inhibitor (TNFα sticky-trap) that can be inducibly expressed by grafted cells, and illustrate the positive therapeutic effect of these biologics on the development of experimental arthritis. We believe that the combination of our cell safety and biologics technology could substantially improve the treatment of degenerative diseases such as arthritis.