COVID-19 diagnostic testing, delivering small molecules to pancreatic beta cells, improved base editing, and profiling Cas9 variant specificity.
Research Roundup: March 20, 2020
Welcome to the March 20, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Broad joins the effort in Massachusetts to ramp up COVID-19 diagnostic testing
The Broad Institute is working closely with the departments of pathology at Massachusetts General Hospital, Brigham and Women's Hospital, and other area hospitals to put Broad's high-throughput genomic capabilities at the disposal of the Commonwealth to enable increased capacity for COVID-19 diagnostic testing. We expect to have the capacity up and running by early next week. Once operational, the Institute expects to be able to process samples collected in hospitals and other clinical settings, and to process more than 1,000 tests a day. Learn more in a story and video on Broad’s COVID-19 work, and coverage from WBUR, WCVB, and MassLive.
Going all metal on diabetes
The ability to precisely target delivery of small molecules to the pancreas's beta cells would be a boon to many avenues of type 1 and type 2 diabetes research. Miseon Lee, Basudeb Maji, Debasish Manna, associate member Amit Choudhary, and colleagues in the Chemical Biology and Therapeutics Science Program and elsewhere have leveraged beta cells' unusually high concentration of zinc to develop what they call a zinc-based prodrug system. The method puts zinc to work to help deliver and activate otherwise inactive small molecule cargoes specifically within beta cells. Learn more in the Journal of the American Chemical Society.
In Nature Biotechnology, a team led by Michelle Richter, Kevin Zhao, and core institute member David Liu in the Merkin Institute for Transformative Technologies in Healthcare describes a new adenine base editor that can fix mutations in the genome more efficiently and at many more target sites compared to its predecessor, unlocking access to correct more genetic variants associated with human diseases. The new editor, called ABE8e, can convert A•T base pairs to G•C far faster than the original editor and has a much wider range of compatibility with the different CRISPR proteins needed to access targets throughout the genome. Learn more in a Broad news story and coverage in GenomeWeb.
Profiling Cas9 variant specificity
Jonathan Schmid-Burgk, Linyi Gao, David Li, core institute member Feng Zhang, and their colleagues have developed a method that scalably detects double-stranded breaks (DSBs), such as off-target ones generated by CRISPR nucleases. The method, tagmentation-based tag integration site sequencing (TTISS), builds on the genome-wide, unbiased identification of double-strand breaks (DSBs) enabled by sequencing (GUIDE-seq), which tags DSBs induced by nuclease cleavage through integration of a double-stranded donor DNA, but the team’s method uses guide multiplexing and bulk tagmentation by Tn5. The team comprehensively assessed Cas9 variants, revealing a trade-off between specificity and activity, and identifying LZ3 Cas9, a variant with high specificity. Learn more in Molecular Cell.