Interdisciplinary Initiatives Program Round 12 - 2024


Project Investigators:

Alice Ting, Genetics and Biology
Xiaojing Gao, Chemical Engineering


Abstract:

This project proposes a novel approach to enhance the safety and effectiveness of protein- and cell-based therapies, such as CAR T-cells used in cancer treatments. Our team proposes to harness proteases, enzymes that can cut proteins, to create a sophisticated control mechanism. This allows the CAR T-cells or therapeutic proteins to be more precisely regulated, increasing their beneficial effects and reducing unwanted side effects. One key objective is to modify a human protease known as Renin, minimizing potential immune reactions and making it more controllable with a small-molecule inhibitor. We also plan to make this engineered Renin sensitive to specific biological 'triggers,' allowing the therapy to be activated only in certain conditions or locations in the body. The expected outcomes of this project, which combines chemical biology (Ting) and synthetic biology (Gao) expertise, will be new candidate therapies ready for further testing, and a robust method for enhancing other protease-based therapies. This research can lead to more effective and safer treatments for various conditions, such as cancer immunotherapy.