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Bacterial CRISPR–Cas systems provide adaptive immunity against phage by transcribing interfering RNA from phage DNA inserted into the bacterial genome. Using deep-sequencing, the authors detect a bias in the phage genome locations sampled, suggestive of selection.

Leveraging RNA-targeting dCas13d enables selective interference with phage protein translation and facilitates measurement of phage gene fitness at a transcriptome-wide scale.

Genome engineering has a new tool—endonucleases involved in bacterial adaptive immunity that can be reprogrammed with customizable small, noncoding RNAs.

In this Review Article, Horvath and Barrangou describe the discovery of CRISPR–Cas systems as mechanisms of adaptive immunity in prokaryotes and explore the technological applications that have emerged from studying these molecular machines.

Infection by defective bacterial viruses that cannot replicate has now been found to be the key feature enabling bacteria to rapidly develop adaptive immunity against functional viruses.

The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems are immunity systems that are present in many bacteria and archaea. Here, Koonin and colleagues present a new classification of these systems and introduce a new nomenclature of the genes in the CRISPR–casloci that better reflects the relationships between the proteins.

A CRISPR-Cas13 enzyme is shown to have potent anti-phage activity that is harnessed to produce a phage genome engineering method with broad utility.

Bile salt hydrolases encoded by the gut microbiome shape the bile acid pool, including microbial conjugated bile acids, which impact Clostridioides difficile infection in the murine gut.

A suite of methods enables programmable species- and locus-specific editing of bacteria in communities.

Type I CRISPR–Cas systems, the largest group of CRISPR systems in nature, can be repurposed for DNA targeting and gene regulation in human cells

Lactobacillus is a lactic acid bacteria and has a wide range of application from use in probiotic food production to biotherapeutics. Here, the authors sequence and compare the genomes of 213 different Lactobacillusstrains and related genera, and provide new insight into phylogenomic organization and adaptive immunity elements in this bacteria family.

CRISPR/Cas is a microbial immune system that is known to protect bacteria from virus infection. These authors show that the Streptococcus thermophilus CRISPR/Cas system can prevent both plasmid carriage and phage infection through cleavage of invading double-stranded DNA.

Bacteria encode many strategies to prevent or escape infection. Through the analysis of metagenomic dark matter, several novel defence systems were identified, some of which were engineered and characterized in vivo, showing that they provide resistance against viruses and plasmids.

Lignocellulose is a promising feedstock to produce bioenergy and biomaterials. Here, the authors review current efforts, including genome editing informed by machine learning, for lignocellulosic feedstock-based bioenergy and biomaterials production and provide outlook for improving feedstock traits.

CRISPR spacers can recombine with phage target sequences to mediate a form of specialized transduction that can promote transfer of CRISPR elements to other bacteria in the population.

CRISPR–Cas systems provide bacteria and archaea with adaptive immunity to invading foreign DNA. In an Analysis article, Koonin and colleagues update a previous classification of these systems to incorporate the large volume of genomic data generated in recent years.

Gene editing may shape the future of foods, providing a sustainable solution for obtaining food products of high yield and nutritional value. This Review discusses the capabilities and applications of CRISPR–Cas-based gene editing of food, highlighting the technologies for improving the nutritional value of crops and animal and probiotic food products, and summarizing regulatory policies worldwide.

The number and diversity of known CRISPR–Cas systems have substantially increased in recent years. In this Review, Koonin and colleagues provide an updated evolutionary classification of CRISPR–Cas systems and cas genes, with an emphasis on major developments, and outline a complete scenario for the origins and evolution of CRISPR–Cas systems.

The unique capabilities of CRISPR technologies have enabled a broad range of applications in biomedicine and agriculture.

Class 2 CRISPR-Cas systems are widely used in genome editing. Joshua Young1, Stephen Gasior et al. now engineer the type I-E Cascade complex from S. thermophiles, optimize the system for expression and nuclear localization in Zea mays and show it compares favorably with Cas9 as a RNA-guided transcriptional activator.

Two recent papers in Science illustrate how the prokaryotic CRISPR-Cas immune system machinery, which typically targets invasive genetic elements such as viruses and plasmids, can be converted into a sophisticated molecular tool for next-generation human genome editing. The versatile Cas9 RNA-guided endonuclease can be readily reprogrammed using customizable small RNAs for sequence-specific single- or double-stranded DNA cleavage.