Ultrasound spatiotemporally enables prolonged therapeutic mRNA translation in engineered bacteria for enhanced cancer immunotherapy.

ABSTRACT: Rationale: Engineered bacteria have recently emerged as a novel and promising strategy for cancer immunotherapy. Nonetheless, precise spatiotemporal regulation of therapeutic gene expression within these bacteria is essential to optimize therapeutic efficacy while minimizing adverse effects. This study aims to develop a system for precise, ultrasound-driven regulation of gene expression in bacteria to enable targeted tumor therapy. Methods: A modular system (Stabilized Open RNA thermometer, SORT) was designed, comprising a modified RNA thermometer with QKI response elements (QRE), therapeutic coding sequences, and the RNA binding motif of QKI. As a proof-of-concept, the bacteria VNP20009 was engineered with plasmids expressing mutated IL-2 or soluble PD-1 (sPD-1) within the S

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12486422 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature