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CRISPR-Cas3

CRISPR-Cas3

CRISPR-Cas3 is a CRISPR protein complex that degrades foreign DNA. It uses an RNA guided protein complex called Cascade to recognize the target DNA sequence and the associated Cas3 protein to degrade the targeted sequence.

CRISPR-Cas3 is a CRISPR protein complex that functions as part of the immune system in bacteria to degrade foreign DNA. Type I CRISPR systems use a protein complex called the Cascade surveillance complex which carries the guide RNA looking for matching viral DNA . Upon finding a match, the Cas3 protein is recruited to degrade the target DNA . This differs from Type II systems such as CRISPR-Cas9 which have the surveillance and cutting properties within the same protein . Charlmin Joo and Stan J.J. Brouns at Delft University of Technology, Netherlands used single-molecule FRET to show that Cas3 repeatedly reels in the target DNA like a biological fishing rod .

Since CRISPR-Cas3 shreds up DNA as opposed to slicing like CRISPR-Cas9 does, it is less useful in genome editing than CRISPR-Cas9 . Working towards improving the usefulness of CRISPR-Cas3 for biomedical applications, Ailong Ke and Maofu Liao of Cornell University and Harvard respectively, used cryo-electron microscopy to show in near-atomic resolution the process of CRISPR-Cas3 loading target DNA and preparing to cut . The images shed light on the mechanisms of action for CRISPR-Cas3 and other CRISPR-Cas systems which can guide researchers in improving the usefulness of these systems in biotechnology.

Paul Garofolo, previously with Caribou Biosciences, and Rodolphe Barrangou, previously with Valeant Pharmaceuticals, cofounded Locus Biosciences, a company that is harnessing the CRISPR-Cas3 DNA shredding activity to kill antibiotic resistant bacteria . Like CRISPR-Cas9, CRISPR-Cas3 the guide RNA sequence can be engineered to target specific DNA sequences. Locus Biosciences is developing antimicrobials by directing CRISPR-Cas3 to shred the DNA of specific pathogenic bacteria. Unlike conventional antibiotics which generally kill both good and bad bacteria, CRISPR-Cas3 based antimicrobials would more specifically target the harmful bacteria .

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Ailong Ke

CRISPR-Cas3 researcher

Charlmin Joo

CRISPR-Cas3 researcher

Maofu Liao

CRISPR-Cas3 researcher

Paul Garofolo

Co-founder of Locus Biosciences

Rodolphe Barrangou

Co-founder of Locus Biosciences

Stan J.J. Brouns

CRISPR-Cas3 researcher

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