%0 Journal Article
%T Sonogenetics-controlled synthetic designer cells for cancer therapy in tumor mouse models.
%A Gao T
%A Niu L
%A Wu X
%A Dai D
%A Zhou Y
%A Liu M
%A Wu K
%A Yu Y
%A Guan N
%A Ye H
%J Cell Rep Med
%V 5
%N 5
%D 2024 May 21
%M 38608697
%F 16.988
%R 10.1016/j.xcrm.2024.101513
%X Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.