Packaging RNA for delivery, a bacterial frenemy, esophagus inflammation explored, and more
By Broad Communications
Credit: Susanna M. Hamilton
Welcome to the August 20, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
A new delivery method for RNA therapeutics
Current gene therapy delivery platforms can be immunogenic, which limits their application in humans. To overcome this, Michael Segel, Blake Lash, Rhiannon Macrae, core institute member Feng Zhang, and colleagues have developed a modular RNA delivery platform that harnesses the human retroelement-derived protein PEG10 to deliver therapeutic RNAs to cells called SEND. The team hopes SEND will have reduced immunogenicity compared to currently used vectors, while also being able to efficiently deliver RNA to a number of different cell types in the body. Read more in Science, a Broad news story, and coverage by STAT and New Scientist.
SPACECAT stalks single cells
One of the biggest challenges in single-cell -omic studies is retaining information about where individual cells resided in their native tissues. Of the methods that exist, most require killing the cells during the preparation process. Alex Genshaft, Carly Ziegler, Constantine Tzouanas, institute member Alex Shalek of the Klarman Cell Observatory, and colleagues have developed a new spatial -omics approach called SPACECAT that allows scientists to fluorescently tag individual living cells in a tissue or organoid, track them over time, and isolate them for molecular profiling, all while recording their position. Learn more in Nature Communications and a tweetorial by Tzouanas.
Bxa: Foe, friend, and fitness factor
Scientists have thought that bacterial ADP-ribosyltransferases (ADPRTs) are toxins involved in pathogenesis. But research scientist Eric Brown, Hugo Arellano-Santoyo (now at Novartis Venture Fund), core institute member Ramnik Xavier in the Infectious Disease and Microbiome Program and colleagues have found that these proteins are common in commensal bacteria in the gut microbiome and often linked with phage elements. The team found that Bxa, an abundant ADPRT in Bacteroides, is secreted and can ADP-ribosylate non-muscle myosin II proteins. In epithelial cells, Bxa remodeled the actin cytoskeleton and caused secretion of inosine, which is used as a carbon source by a Bxa-encoding Bacteroides to colonize the gut in high numbers. The results suggest that ADPRTs may act as bacterial fitness factors. Read more in Cell Host & Microbe.
New clues to the causes of food allergy disease
Food allergies can trigger eosinophilic esophagitis (EoE), a disease that leads to chronic inflammation of the esophagus and pronounced difficulty eating. To uncover the cell types and mechanisms that drive inflammation in EoE, Duncan Morgan, associate member Christopher Love, and colleagues in the Cancer Program used single-cell sequencing techniques in different tissues from patients with EoE. They found cell types and signaling pathways that were elevated in the esophagus of patients with active disease and pinpointed the molecule that triggers immune cells to target the esophagus. These results provide new insights into the immune response during EoE. Read more in Science Immunology.
A deeper look at the immunopeptidome
Identifying antigens presented on the surface of tumor cells is an important step in developing immunotherapies. Mass spectrometry is the most effective method to directly identify these molecules; however, it often requires 500 million or more cells, which cannot be collected from a typical clinical tumor sample. A team led by Susan Klaeger and institute scientist Steven Carr, senior director of Proteomics, has now developed a method with increased sensitivity: microscaled basic reversed-phase fractionation, followed by ion mobility coupled to mass spectrometry. The new approach could help improve prediction algorithms and enable detection of additional clinically relevant molecules. Read more in Molecular & Cellular Proteomics.