In the early, online edition of Proceedings of the National Academy of Sciences, investigators from the University of Massachusetts and Tufts University demonstrate the feasibility of establishing a mouse model of genetically-induced emphysema using CRISPR/Cas9-based editing to lop out half a dozen paralogs of Serpina1 — a gene implicated in alpha-1 antitrypsin deficiency (AAT)-related forms of emphysema in humans. "The phenotype recapitulates the human disease phenotype," the authors write, adding that "[w]e anticipate that this unique model will be highly relevant not only to the preclinical development of therapeutics for AAT deficiency, but also to emphysema and smoking research."
A University of California, Los Angeles-led team explores the potential for altering DNA methylation patterns at specific targets in Arabidopsis, focusing first on cytosine methylation at a relatively well-studied "flowering Wageningen" (FWA) gene promoter. In particular, the researchers showed that they could do targeted demethylation on FWA by targeting the catalytic domain of a TET1 human demethylase to the gene's promoter with an artificial zinc finger. The resulting demethylation at this locus led to a rise in FWA expression and a related flowering phenotype, they report. More broadly, the authors say, these and other results in Arabidopsis suggest that such strategies "can be used to approach basic questions about DNA methylation biology, as well as to develop new biotechnology strategies to modify gene expression and create new plant trait epialleles."
Researchers from Massachusetts General Hospital, the Dana Farber Cancer Institute, and elsewhere describe circulating melanoma cell gene expression signatures that appeared to predict response to PD-1/PD-L1 immune checkpoint blockade drugs. With the help of available data from GTEx and the Cancer Genome Atlas — together with RNA sequences for white blood cells from individuals with or without melanoma — the team narrowed in on a quantitative 19-gene circulating tumor cell score that successfully picked out melanoma cells in dozens of microfluidics-enriched patient blood samples. Using droplet digital PCR and microfluidic circulating tumor cell (CTC) enrichment, the authors followed this "CTC score" in samples from 49 individuals with melanoma during immune checkpoint treatment, identifying progression-free survival-related dip in CTCs in the first two months of treatment.