Skip to main content
Premium Trial:

Request an Annual Quote

PNAS Papers on Mosquito Gene Drive, Head and Neck Cancer, Precancerous Lesions in Lung

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted this week.

A team from the UK, US, and Italy explores off-target edits in an Anopheles gambiae malaria mosquito model subjected to a CRISPR-Cas9-based gene drive, using a germline-incorporated version of the Cas9 nuclease enzyme designed to prompt "super-Mendelian inheritance of the transgene by homology-directed repair." Based on their "circular in vitro reporting of cleavage sites by sequencing" (CIRCLE-seq) and targeted deep sequencing experiments on samples from three Anopheles mosquito gene drive populations, the investigators estimated that off-target mutations occur up to 1.42 percent of the time, though those off-target changes do not appear to be subject to the gene drive in the mosquitos. "The findings of this study represent an important milestone for the understanding and managing of CRISPR-Cas9 specificity in mosquitos," they write, "and demonstrates that CRISPR off-target editing in the context of a mosquito gene drive can be reduced to minimal levels."

Investigators at the University of Texas MD Anderson Cancer Center and elsewhere report on findings from an analysis of human papillomavirus (HPV)-negative head and neck squamous cell carcinomas, particularly a so-called "immune paradox" that involves immune suppression in somatic copy number alteration-rich tumors that prompt cytotoxic immune responses in precancerous forms of the disease. From genomic data generated for the Cancer Genome Atlas project, along with molecular profiles on 188 HPV-negative oral precancer cases and dozens of cell lines, the team found that specific deletions involving chromosome 9p and related JAK-STAT pathway deletions not only drive the transition from oral precancers to cancer, but also dial down cytotoxic T cell activity against tumors as well as response to anti-PD-1 immune checkpoint blockade immunotherapy.

A Boston University-led team digs into precancerous lesions that turn up in bronchial tissue prior to lung squamous cell carcinoma development. Using RNA sequencing, immunohistochemistry, and other experiments in mouse models and cell cultures, the researchers saw signs that polarity within bronchial epithelial cells helps to maintain homeostasis, while conditional deletion of a gene called CRB3 led enhanced activity of the transcriptional regulators YAP and TAZ. That, in turn, prompted them to explore the consequences of deleting YAP or TAZ or inhibiting ERBB receptors targeted by YAP/TAZ-regulated genes, which appeared to repair pre-cancerous growth. "Genetic deletion of YAP/TAZ or pharmacological inhibition of ERBB receptors prevents and treats pre-cancer airway lesion development following lung epithelial damage," they write, "offering important knowledge that may guide therapeutic strategies for intercepting the development of squamous lung cancers."

The Scan

Algorithm Teases Out Genetic Ancestry in Individuals at Biobank-Scale

Researchers establish an algorithm known as Rye to tease apart ancestry fractions in admixed individuals at a biobank-scale, applying it to 488,221 UK Biobank participants in Nucleic Acids Research.

Multi-Ancestry Analysis Highlights Comparable Common Variants at Complex Trait-Linked Loci

Researchers in Nature Genetics examine common variants implicated in more than three dozen conditions, estimating genetic effect similarities across ancestry tracts in admixed individuals.

Sick Newborns Selected for WGS With Automated Pipeline

Researchers successfully prioritized infants with potential Mendelian conditions for whole-genome sequencing or rapid whole-genome sequencing, as they report in Genome Medicine.

Acne-Linked Loci Found Through GWAS Meta-Analysis

Researchers in the European Journal of Human Genetics find new and known acne vulgaris risk loci with a genome-wide association study and meta-analysis, highlighting hair follicle- and metabolic disease-related genes.