Researchers from Boston Children's Hospital, Harvard Medical School, and Northeastern University present a proof-of-principle study of a non-viral delivery method for editing triple-negative breast cancer (TNBC) genomes. The non-cationic, deformable, tumor-targeted nanolipogel (tNLG) system covers, delivers, and releases CRISPR plasmids to specific cell sites with the help of antibody guides and other delivery tweaks, the team explains. The authors used tNLG and CRISPR-Cas9-based editing to knock out the oncogene lipocalin 2 in human TNBC cells and in orthotopic TNBC tumor tissue models. In those experiments, this genome editing-based nanotherapy approach seemed to dial down TNBC cell aggressiveness and human TNBC growth in mice. "Our results provide experimental evidence that in vivo CRISPR genome editing can halt TNBC tumor progression," they report.
Sequence variants in the vacuolar protein sorting 13A gene VPS13A seem to contribute to migration differences between songbirds in Central America and their counterparts in South America, according to a team from Pennsylvania State University, the University of Colorado, the University of Toledo, and Cornell University. The researchers re-sequenced 70 golden-winged warblers (Vermivora chrysoptera) or blue-winged warblers (V. cyanoptera), comparing SNPs in birds that spend their winters in Central or South America, based on geotracking data or breeding location-based predictions. Their search highlighted a stretch of Z chromosome sequence showing allele frequencies differences between the Central and South American songbirds — a VPS13A-containing region with muted genetic variation in warblers wintering in South America. "In humans, variants of VPS13A are linked to the neurodegenerative disorder chorea-acanthocytosis," the authors note. "This association provides one of the strongest gene-level associations with avian migration differences."
Also in PNAS this week, researchers at Purdue University and elsewhere search for microRNAs involved in neutrophil migration, a process involved in inflammatory immune responses to pathogens or other immune stimuli. Using zebrafish embryo models, the team sequenced miRNAs found in neutrophil cells and in immotile epical keratinocyte cells, before over-expressing the neutrophil-specific miRNAs to screen for neutrophil migration suppressors. The search led to eight miRNAs that seemed to quash neutrophil movement in zebrafish, including miR-199, an miRNA that seemed to suppress chemotaxis in neutrophil-like human cells by inhibiting the cyclin-dependent kinase 2 (Cdk2). "Together, our work suggests miR-199 and CDK2 as new targets for treating inflammatory ailments, and introduces an avenue of the function for CDK2 outside [of] cell cycle regulation," the authors write.