Genetic Engineering Publications - GEG Tech top picks

Researchers examined two cohorts of patients who received CD19-directed CAR-T cells for non-Hodgkin's lymphoma or B-cell acute lymphoblastic leukemia. The researchers used the first cohort to retrospectively examine the impact of prior antibiotic use on CAR-T clinical outcomes. The second cohort had prospective baseline fecal samples collected before CAR-T cell infusion for subsequent assessment of the fecal microbiome. The investigators determined that the use of certain antibiotics including piperacillin/tazobactam, meropenem, and imipenem/cilastatin, negatively affected OS (HR = 1.71; 95% CI, 1.12-2.59). The investigators also noted a significantly increased risk of immune effector cell-associated neurotoxicity syndrome among the entire cohort evaluated for pre-CAR-T antibiotic use (P = 0.023). Stool samples from the prospective cohort demonstrated an altered fecal microbiome including lower alpha diversity, increased frequency of bacterial dominance, and altered bacterial composition compared with healthy controls. The results of this study suggest that the composition of the gut microbiome affects CAR-T outcomes, but the investigators cautioned that further prospective studies in larger patient populations are needed to confirm the associations.

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.

NU iGEM is creating a delivery system for an innovative antibiotic method centered around CRISPR, a powerful gene editing tool. With CRISPR, researchers can design guide RNA to direct the protein Cas9 to cut out any gene from a cell. In our case, we will target antibiotic resistance genes, leaving pathogens defenseless. They want to harness the natural messenger properties of bacterial outer membrane vesicles (OMVs) to package Cas9 and deliver it to cells as a biological Trojan Horse.

The treatment of bacterial infections depends on the effectiveness of current antibiotic therapy, but this is seriously threatened by the growing problem of antibiotic resistance. The US Centers for Disease Control and Prevention estimates that more than 2.8 million antibiotic-resistant infections occur each year in the US, while the European Centre for Disease Prevention and Control reports more than 670M resistant infections per year in the EU, with estimated healthcare costs of approximately €1.1 billion. In a recent study, researchers from Dr. S. Rodrigue of the University of Sherbrooke, Quebec, Canada describes a novel probiotic conjugative strain of E. coli that can propagate a CRISPR-Cas9 system with high transfer rates in the gut microbiota of mice. The scientists screened families of conjugative plasmids in Enterobacteriaceae and identified plasmid TP114 as an efficient DNA transfer machine in the mouse gut microbiota, first integrated a CRISPR-Cas9 module into the TP114 conjugative plasmid, and then introduced the resulting construct into a donor probiotic conjugative E. coli strain. They demonstrated that their new system could eliminate an antibiotic-resistant gastrointestinal infection in mice, raising hopes for new ways to treat antibiotic-resistant infections.

Researchers from Inserm and Université de Rennes recently identified a new bacterial toxin which they transformed into potent antibiotics active against various bacteria responsible for human infections.

Novel antibiotics effective against gram-positive and -negative multi-resistant bacteria with limited resistance