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, the CRISPR-Cas3 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 .
Co-founder of Locus Biosciences
Co-founder of Locus Biosciences
Stan J.J. Brouns
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- Cluster: Synthetic biologyA cluster of topics related to synthetic biology.
- Cluster: BiotechnologyA cluster related to biotechnology.
- CRISPR/Cas ToolsClustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated (Cas) proteins perform adaptive immune functions in prokaryotic organisms defending against foreign nucleic acids such as viruses. CRISPR/Cas tools have been adapted for use in genome editing and other DNA and RNA targeting applications.
- CRISPRClustered regularly interspaced short palindromic repeats (CRISPR) is a prokaryotic adaptive immune response that provides immunity against foreign nucleic acids, such as viral DNA and bacterial plasmids, through the use of crRNAs (CRISPR RNAs) and associated Cas genes.
- CRISPR-Cas13A nucleic acid editing technology that targets RNA, analogous to the CRISPR-Cas9 system
- CRISPR-Cas12aCRISPR-Cas12a is is a genome editing tool similar to CRISPR-Cas9. CRISPR-Cas12a is a set of RNA guided DNA targeting proteins capable of producing targeted double-stranded DNA (dsDNA) breaks, targeted single-stranded DNA breaks, and indiscriminate ssDNA degradation in trans. The effector protein Cas12a is also known at Cpf1.