Locus Biosciences


Locus Biosciences is a preclinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina which aims to develop phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Case9, delivered by engineered bacteriophages, under the trademark crPhage. The intended therapeutic target of crPhase is antibiotic-resistant bacterial infections.

History

The company was founded as a spin-off from North Carolina State University in 2015 with a $5 million convertible note from the Chinese investor Tencent Holdings and North Carolina Biotechnology Center, and licensed CRISPR patents from NCSU.
In 2017, the company closed a $19 million Series A led by Artis Ventures, Tencent Holdings Ltd, and Abstract Ventures.
In 2018, Locus acquired the high-throughput bacteriophage discovery platform from San Francisco-based phage therapy company Epibiome, Inc.
In 2019, the company entered into a strategic collaboration with Janssen Pharmaceuticals worth up to $818 million to develop CRISPR-Cas3 drugs targeting two bacterial pathogens.
Under the terms of the partnership, Locus will receive $20M upfront and up to $798M in milestones and royalties on net sales.

Differences between CRISPR CAS 3 and other subtypes

CRISPR-Cas3 is more destructive than the better known CRISPR–Cas9 used by companies like Caribou Biosciences, Editas Medicine, Synthego, Intellia Therapeutics, CRISPR Therapeutics and Beam Therapeutics. CRISPR–Cas3 destroys the targeted DNA in either prokaryotic or eukaryotic cells. Co-founder, Rodolphe Barrangou, said "Cas3 is a meaner system...but if you want to cut a tree and get rid of it, you bring a chain saw, not a scalpel"
CRISPR-Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is divided into types II, V, and VI. The 6 system types are divided into 19 subtypes. Many organisms contain multiple CRISPR-Cas systems suggesting that they are compatible and may share components.
ClassCas typeSignature proteinFunctionReference
1ICas3Single-stranded DNA nuclease and ATP-dependent helicase
2IICas9Nucleases RuvC and HNH together produce DSBs, and separately can produce single-strand breaks. Ensures the acquisition of functional spacers during adaptation.

Clinical trial

The company enrolled its first patient in a Phase 1b clinical trial in January, 2020. The trial intends to evaluate LBP-EC01, a CRISPR Cas3-enhanced bacteriophage against Escherichia coli bacteria which cause urinary tract infections. Twenty patients will get a phage cocktail, and 10 will get a placebo.