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crPhage: Novel Antimicrobials Based on CRISPR-Cas3

Part of the BTEC Spring 2020 Seminar Series

Kurt Selle, Ph.D.
Senior Scientist Group Lead, Locus Biosciences, Inc.

Seminar description

New and novel antibacterial therapies are needed urgently to counter the continually evolving threat of antimicrobial-resistant bacterial infections including multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacterial infections. CRISPR-Cas systems are DNA-encoded, RNA-mediated, nucleic-acid-targeting adaptive immune systems against infectious genetic elements in bacteria. However, when redirected to target bacterial DNA, CRISPR-Cas systems exhibit potent antimicrobial activity by irreparably degrading the bacterial genome. Across different CRISPR-Cas, Type I systems are uniquely suited for antimicrobial potency due to activity of the signature nickase-helicase-exonuclease protein, Cas3.

Locus Biosciences is a clinical-stage biopharmaceutical company that is developing antibacterial therapies using engineered bacteriophages, known as crPhage, which act via destruction of the bacterial genome by CRISPR-Cas3 and by phage-mediated lysis. Its modular drug development platform enables the design and creation of powerful antimicrobial crPhage cocktails with high potency and favorable safety profiles that enable rapid regulatory clearance. Generally, crPhages can readily be delivered by multiple routes of administration and exhibit high systemic concentrations sufficient for antimicrobial activity in vivo, but are also self-limiting in the absence of infection and clear rapidly. Locus is advancing its platform to create therapeutics for critical disease areas ranging from resistant bacterial infections to chronic conditions exacerbated or caused by microbiome-associated bacteria. Locus technology is uniquely suited for microbiome targets due to the unique narrow-spectrum profile of its drug products. In conclusion, CRISPR-Cas3 antimicrobial technology can be broadly applied across high priority infectious disease agents and other emergent bacterial pathogens with a novel anti-bacterial modality.

Dr. Selle earned his doctorate in functional genomics at North Carolina State University under the direction of Rodolphe Barrangou and Todd Klaenhammer. The primary outcome of his research was using bacterial genome targeting CRISPR to capture large genomic deletions, leading to an awarded patent. He then joined Locus Biosciences in 2016 to develop and commercialize the patented technology and is now a senior scientist and group leader of Synthetic Biology.