Genome editing and precision engineering of probiotic strains: A narrative review
Probiotics contribute to gut homeostasis, immune regulation, metabolic balance, and host–microbiome signaling, but the clinical performance of conventional strains remains inconsistent because of limited gastrointestinal survival, strain-specific functionality, host-dependent variability, and incompletely understood mechanisms of action. This narrative review examines how genome editing and synthetic biology are being applied to address these constraints in probiotic engineering. We compare six genome-engineering technologies used in probiotic strain development— CRISPR-Cas systems, genome shuffling, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), base editing, and prime editing — against six criteria: editing precision, capacity for multitrait optimization, scalability, regulatory readiness, clinical maturity and best-suited application. The comparison reflects a literature-based, expert-synthesized assessment rather than a validated quantitative or clinically derived scoring system, and technology maturity is found to vary widely: CRISPR-Cas systems are the most extensively characterized in probiotic hosts, genome shuffling remains a recombination-based strain-improvement approach rather than precision editing, and base and prime editing are still largely at an early, species-dependent stage of development in bacteria. The review also considers translational barriers, including biosafety concerns such as off-target editing and horizontal gene transfer, heterogeneous regulatory classification of engineered strains across jurisdictions, manufacturing and strain-stability constraints, and the current scarcity of controlled human clinical data for genome-edited probiotics as distinct from conventional probiotic supplementation. We conclude that no single technology is sufficient on its own, and that combining complementary editing approaches with multi-omics and computational tools, alongside standardized safety testing and clearer regulatory pathways, will be necessary before precision-engineered probiotics can move from preclinical and early-stage research into validated live biotherapeutics.
Nagarkar R, Kovaleva E, Dahikar S, and Bhutada S. Genome editing and precision engineering of probiotic strains: A narrative review. J Appl Biol Biotech 2026. Article in Press. http://doi.org/10.7324/jabb.2026.321621
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Year
Month
Engineering exosome-based gene therapies: Tools, targets, and AI-enabled genomic design
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