CRISPR–Cas therapies targeting bacteria

Abstract

Technologies derived from the CRISPR (clustered regularly interspaced short palindromic repeats)–Cas immune system of prokaryotes have revolutionized our ability to cleave and modify target nucleic acid sequences. In addition to the use of CRISPR–Cas tools for the editing of human genes, they can also be designed to target pathogenic and commensal bacteria that colonize the body, offering new pathways for the treatment of infections and microbiome modulation. In this Review, we explore how the CRISPR–Cas toolbox can be engineered to kill or modify specific bacteria. We discuss DNA-targeting and RNA-targeting strategies, outlining how these can be applied to disarm bacteria by removing, modifying or silencing specific genes. Furthermore, we examine the delivery of CRISPR–Cas tools by bacteriophages and through conjugation and explore intracellular barriers to CRISPR–Cas tool maintenance and expression. Finally, we highlight therapeutic opportunities in the treatment of infectious diseases and for the modification of the microbiome, outlining progress and challenges in translating these approaches into clinical applications. CRISPR–Cas tools can be designed to kill or modify specific bacteria. This Review explores the engineering of CRISPR–Cas tools and corresponding delivery strategies for the treatment of bacterial infections and modification of the microbiome.