Genetic Engineering Publications - GEG Tech top picks

The emergence of antibiotic-resistant pathogens represents a major global challenge. In numerous disease areas, current medical practice relies on increasingly aggressive therapies, which can sometimes result in patients experiencing life-threatening infections, including those caused by antibiotic-resistant bacteria. SNIPR001's mechanism of action, as a CRISPR-armed phage therapeutic that specifically targets and eradicates E. coli in the gut, is designed to prevent infections from spreading into the bloodstream and represents a promising advancement against antibiotic-resistant pathogens. This publication represents a significant validation of the ground-breaking technology research done at the laboratories and collaborators of SNIPR Biome, the company pioneering CRISPR-based microbial gene therapy, and also opens up the possibility of targeting other pathogens.  SNIPR001 has been granted a Fast-Track designation by the US Food and Drug Administration, was supported by CARB-X, and SNIPR is currently conducting a Phase 1 trial in the US to evaluate its safety and efficacy in reducing E. coli in the gut without disturbing the overall gut microbiome. 

Here, the authors develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9 delivered by a bacteriophage. They show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.

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.

For the first time, researchers have solved the structure of viral anti-CRISPR proteins attached to a bacterial CRISPR surveillance complex, revealing precisely how viruses incapacitate the bacterial defense system. The research team, co-led by biologist Gabriel C. Lander of The Scripps Research Institute (TSRI), discovered that anti-CRISPR proteins work by locking down CRISPR’s ability to identify and attack the viral genome. One anti-CRISPR protein even “mimics” DNA to throw the CRISPR-guided detection machine off its trail.