By leveraging a self-transmissible plasmid chassis, our approach achieves three key outcomes: (1) efficient horizontal transfer of dCas9-based silencing modules across diverse pks+E. coli, (2) durable repression of clb genes without bacterial killing or mutational escape, and (3) robust suppression of DNA damage, NC101 colonization, and tumor burden in mice. The gene discussed is CLYBL; the disease is neoplasm.