Scientists from the Innovative Genomics Institute at UC Berkeley, North Carolina State University and Lawrence Berkeley National Lab use RNA-targeting CRISPR systems to drive genome editing across phage diversity.
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Bacterial viruses (bacteriophages or phages) are estimated to be among the most diverse and abundant biological entities on earth. As bacterial predators, phages are their host bacteria are locked in a coevolutionary arms race, driving the evolution of phage defense-systems such as CRISPR-Cas and ways to undermine these systems encoded by phages. Because many of the genome editing tools are derived from this arms race, tools for phage genome-editing have limited efficacy. Scientists’ ability to perform genetics in, nonetheless engineer, phages remains inherently limited.
By investigating a rare and unconventional CRISPR-Cas system (Cas13a), researchers from the Innovative Genomics Institute at University of California Berkeley in collaboration with North Carolina State University and Lawrence Berkeley National Lab found phage-encoded defense against Cas13a targeting to be incredibly rare across E. coli phage diversity. By using this broad vulnerability to Cas13a, they were able to establish a robust phage genome-editing practice across phage diversity. Critically, they demonstrated the capacity to perform precise and diverse edits ranging from single codons up to multi-gene deletions.
As a result of this study, researchers are now capable of genome-editing in diverse phages. Use of these findings and tools allows us to easily perform genetics in phages, allowing us to better understand phage-host interactions and discover phage-encoded biotechnological tools. Additionally this study greatly facilitates phage engineering for phage therapy and microbiome engineering.
Adler, B.A.; T. Hessler, B.F. Cress, V.K. Mutalik, R. Barrangou, J.F. Banfield, J.A. Doudna (2022) RNA-targeting CRISPR-Cas13 provides broad-spectrum phage immunity. Nature Microbiology [DOI]:10.1038/s41564-022-01258-x
Contact
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Innovative Genomics Institute
University of California, Berkeley
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Postdoctoral Researcher,
Doudna Lab Innovative Genomics Institute University of California, Berkeley