Authors
Zilin Zhou, Yingming Yang, Fangjie Zhou, Kunneng Liang, Tao Gong, Xinxuan Zhou, Jianshu Li, Jun Luo, Jiyao Li, Jiaojiao Yang
Published in
Science advances. Volume 12. Issue 30. Pages eaef1760. Jul 24, 2026. Epub Jul 24, 2026.
Abstract
Pathogenic infections drive microbial dysbiosis and persistent inflammation, posing therapeutic challenges due to difficulties in precise pathogen eradication and microbiome restoration. Although CRISPR-based therapeutics enable pathogen-specific antibacterial targeting, their effectiveness in treating pathogenic infections is constrained by difficulties in navigating complex microbial ecosystems, penetrating pathogenic barriers, sustaining energy-intensive intracellular cleavage, and, critically, restoring microbial balance after pathogen clearance. Here, we engineer a probiotic vesicle-synergized CRISPR platform by encapsulating gtfB-targeting CRISPR plasmids within hybrid extracellular vesicles from probiotics and pathogenic Streptococcus mutans. The pathogen-derived vesicle component enables targeted uptake by S. mutans, facilitating intracellular cleavage of the virulence gene gtfB. Vesicle-carried endogenous adenosine triphosphate (ATP) boosts CRISPR activity, amplifying targeted DNA cleavage for potent and selective pathogen elimination. Probiotic-derived vesicle components further remodel quorum-sensing networks and immunity, restoring microbial homeostasis. This probiotic vesicle-based strategy integrates ATP-enhanced CRISPR cleavage with microbiome and immune modulation, offering a next-generation therapeutic paradigm for microbiome-associated diseases.
PMID:
42497250
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.
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