Journal of immunoassay & immunochemistryApr 16, 2026

CRISPR-Cas: from natural bacterial defense to precise genetic tools

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 17, 2026

Abstract

CRISPR-Cas systems serve as RNA-guided immune systems in bacteria and archaea, facilitating genome engineering and influencing antimicrobial resistance.

CRISPR-Cas systems mediate sequence-specific defense against genetic elements and have been repurposed for precise genome editing.
The use of CRISPR platforms, particularly Cas9, has advanced functional genomics and drug development, progressing toward clinical applications.
Native and engineered CRISPR-Cas systems play a role in horizontal gene transfer and the emergence of antimicrobial resistance globally.
The review integrates insights into CRISPR-Cas classification, molecular mechanisms, and the impact of cellular DNA repair on editing precision.
Delivery methods such as plasmids, bacteriophages, and nanoparticles are examined, along with evolutionary responses from mobile genetic elements.

Simplified

Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) form RNA-guided adaptive immune systems in bacteria and archaea that mediate sequence-specific defense against invading genetic elements. Beyond their ecological role in restricting bacteriophage infection and horizontal gene transfer (HGT), CRISPR-Cas systems have been repurposed as programmable nucleases, enabling rapid, scalable, and precise genome engineering. Over the past decade, CRISPR platforms, most prominently Cas9, have transformed functional genomics, accelerated target discovery and drug development, and progressed from experimental tools to clinically evaluated gene and cell therapies. In parallel, growing attention has focused on both native and engineered roles of CRISPR-Cas in shaping HGT, plasmid ecology, and antimicrobial resistance (AMR), as AMR continues to expand globally. In this Review, we integrate advances spanning eukaryotic genome editing and prokaryotic antimicrobial applications. We summarize CRISPR-Cas classification and molecular mechanisms, highlighting spacer acquisition, guide RNA biogenesis, target recognition, and nucleic acid cleavage. We then examine how cellular DNA repair pathways influence editing outcomes and discuss strategies to enhance precision. We further review delivery strategies, such as conjugative plasmids, bacteriophages and phagemids, extracellular vesicles, and nanoparticles, together with evolutionary countermeasures encoded by mobile genetic elements, including anti-CRISPR proteins. Finally, we outline current limitations.

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CRISPR-Cas: from natural bacterial defense to precise genetic tools

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