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Nature Studies Present New CRISPR System, Addition of Chromatin Interaction Profiles to Brain Disorder Risk Gene Prediction, More

A new and efficient CRISPR system for genome editing in plants is reported in Nature Plants this week. In the study, a University of Maryland-led team focused on the nuclease Cas12b from various bacteria — Alicyclobacillus acidoterrestris, Alicyclobacillus acidiphilus (Aa), Bacillus thermoamylovorans, and Bacillus hisashi — for genome editing in rice, finding that AaCas12b was the most efficient of the four for targeted mutagenesis. They also engineered the Cas12b systems for targeted transcriptional repression and activation, establishing Cas12b as the third promising CRISPR system, along with Cas9 and Cas12a, for plant genome engineering.

A novel approach for targeted CRISPR-Cas9 genome editing in patient-derived xenografts (PDXs) that expands their use as human cancer models is reported in Nature Cancer this week. The platform, developed by a group of Memorial Sloan Kettering Cancer Center and New York University Langone Health investigators, uses a tightly regulated, inducible Cas9 vector that does not require in vitro culture for selection of transduced cells. The scientists show that it can be used to analyze genetic dependencies by targeted gene disruption, as well as mechanisms of acquired drug resistance by site-specific gene editing using templated homology-directed repair. The platform, they write, represents "a core enabling technology for in vivo functional genomics in PDXs, allowing interrogation of gene essentiality, candidate drug targets, mechanisms of acquired resistance, tumor suppressor function, chemical-genetic interactions, and variants of unknown significance."

Through the incorporation of brain chromatin interaction profiles, a University of North Carolina at Chapel Hill team has improved the ability of the gene and gene-set analysis software MAGMA to predict brain disorder risk genes. As reported in Nature Neuroscience this week, the researchers added chromatin interaction profiles from human brain tissue across two developmental epochs and two brain cell types to MAGMA. The resulting platform — which they call Hi-C-coupled MAGMA, or H-MAGMA — was applied to five psychiatric disorders and four neurodegenerative disorders to reveal biological pathways, developmental windows, and cell types implicated for each.