Energy-assisted CRISPR cleavage and probiotic vesicle signaling platform: Microbiome reprogramming for homeostasis

Zilin Zhou1, Yingming Yang1, Fangjie Zhou1

  • 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Science Advances
|July 24, 2026
PubMed

Insights

This study introduces a novel CRISPR-based therapy using probiotic vesicles to target pathogenic bacteria like Streptococcus mutans. The engineered vesicles enhance CRISPR

Area of Science:

  • Microbiology
  • Biotechnology
  • Genetic Engineering

Background:

  • Pathogenic infections cause microbial dysbiosis and inflammation, presenting treatment challenges.
  • Current CRISPR therapeutics struggle with precise pathogen eradication and microbiome restoration in complex ecosystems.

Purpose of the Study:

  • To engineer a probiotic vesicle-synergized CRISPR platform for effective treatment of pathogenic infections.
  • To overcome limitations of CRISPR-based therapies in pathogen targeting and microbiome restoration.

Main Methods:

  • Encapsulating CRISPR plasmids targeting the gtfB gene into hybrid extracellular vesicles from probiotics and Streptococcus mutans.
  • Utilizing pathogen-derived vesicle components for targeted uptake and probiotic-derived components for immune modulation.
  • Incorporating vesicle-carried adenosine triphosphate (ATP) to enhance CRISPR activity.

Main Results:

  • The engineered vesicles achieved targeted intracellular cleavage of the gtfB virulence gene in S. mutans.
  • Vesicle-carried ATP significantly boosted CRISPR-mediated DNA cleavage, leading to potent and selective pathogen elimination.
  • Probiotic vesicle components modulated quorum-sensing networks and immunity, restoring microbial homeostasis.

Conclusions:

  • The probiotic vesicle-based strategy offers a next-generation therapeutic paradigm for microbiome-associated diseases.
  • This approach integrates enhanced CRISPR cleavage with microbiome and immune modulation for comprehensive treatment.

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