Engineering CRISPR System-Based Bacterial Outer Membrane Vesicle Potentiates T Cell Immunity for Enhanced Cancer Immunotherapy.

ABSTRACT: Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but only benefits a subset of patients because of insufficient infiltration and inactivation of effector T cells. Bacterial outer membrane vesicles (OMVs) can activate immunity and deliver therapeutic agents for immunotherapy. However, efficiently targeting and packaging therapeutic molecules into OMVs remains challenging. Here, the engineered E. coli BL21-derived OMVs enable the packaging of multiple genes, resulting in a 7-fold increase in DNA enrichment efficiency and gene silencing in vitro. Moreover, the engineered OMVs carrying genes encoding CXCL9 and IL12 (OMV-C9I12) reprogram tumor cells to secrete these factors, significantly enhancing T-cell chemotaxis and activation. More importantly, this system marke

SUBMITTER: Wang H 

PROVIDER: S-EPMC12506603 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature