公开(公告)号：US20210324389A1

公开(公告)日：2021-10-21

申请号：US17230998

申请日：2021-04-15

Applicant: California Institute of Technology

Inventor： Mohamad H. Abedi ,  Mikhail Shapiro ,  Dan I. Piraner ,  Justin Lee

IPC: C12N15/63 ,  C07K14/725

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in spatiotemporal regulation of therapeutic T-cells through a combination of molecular and physical actuation. There are provided, in some embodiments, thermal bioswitches that allow T-cells to sense small changes in temperature and use them as inputs for the actuation of genetic circuits. Also disclosed herein are T cell activity sensors. Genetic circuits capable of inducing expression of a payload upon thermal stimulation and/or immune cell stimulation are provided. There are provided, in some embodiments, thermally actuated immune cells and methods of using are provided. Oscillator circuits and methods of preventing T cell exhaustion are also disclosed.