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Locus Biosciences announced on Wednesday that it successfully completed the world's first clinical trial using a CRISPR-enhanced bacteriophage therapy. CRISPR-Cas3 enhanced the virus' natural ability to kill the E. coli bacteria behind urinary tract infections. 
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BigField GEG Tech's insight:
The authors showed atomic resolution structures of a full-length Cas3, revealing how Cas3 coordinates binding, ATP-dependent translocation, and nuclease digestion of invader DNA.
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Scoop.it!
BigField GEG Tech's insight:
Here, the scientists use single-molecule imaging to visualize Cascade and Cas3 binding to foreign DNA targets. Their analysis reveals two distinct pathways dictated by the presence or absence of a protospacer-adjacent motif (PAM). Binding to a protospacer flanked by a PAM recruits a nuclease-active Cas3 for degradation of short single-stranded regions of target DNA, whereas PAM mutations elicit an alternative pathway that recruits a nuclease-inactive Cas3 through a mechanism that is dependent on the Cas1 and Cas2 proteins.
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Locus Biosciences announced that it has completed the world's first clinical trial using a CRISPR-enhanced bacteriophage therapy in which CRISPR-Cas3 improved the natural ability of the virus to kill the E. coli bacteria behind urinary tract infections. The company decided to take a nuclear approach and to become the first company to combine both mechanisms, using both the lytic properties of bacteriophage and the DNA-destroying enzymatic properties of CRISPR-Cas3, thus increasing the killing capacity of naturally lytic phages. The co-founder and Scientific Director of Locus Biosciences explains that the study gives him hope that modified bacteriophages could one day become a new weapon in the fight against the growing threat of antimicrobial resistant strains of bacteria. During Phase I of the randomized, double-blind, placebo-controlled clinical trial called LBP-EC01, the research team did not see a single drug-related adverse event throughout the experiment. Phage therapy therefore has no impact at all on human cells. As a result, it is a much more accurate tool for killing bacteria than broad-spectrum antibiotics or other therapies currently in use. More importantly, data suggest that it is safe for humans, even at high doses. Phase II will therefore begin shortly.