The researchers loaded plasmids encoding Cas9 and a guide targeting the essential gtfB virulence gene into mesoporous silica nanoparticles. These were coated with extracellular vesicles from S. mutans and probiotic Lactobacillus, enabling uptake by the pathogen. CRISPR-Cas9 cleavage created double-strand breaks that S. mutans could not efficiently repair, causing bacterial death rather than heritable gene editing.
ATP carried by the vesicles supported bacterial energy metabolism and increased CRISPR-mediated killing to more than 72.3%. In mixed biofilms and saliva from people at high risk of caries, the treatment reduced S. mutans while preserving S. sanguinis and S. gordonii and enriching beneficial bacteria.
In a rat caries model, treatment reduced enamel demineralisation, biofilm thickness and lesion scores over 41 days. Probiotic vesicle components also suppressed inflammatory signalling in cultured macrophages and promoted repair in an acid-induced model of oral mucositis. Variation between vesicle preparations could, however, affect delivery, ATP content and reproducibility.
The study was led by Zilin Zhou, Jun Luo, Jiyao Li and Jiaojiao Yang at Sichuan University. It was published in Science Advances on 24 July 2026.
