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Duke University Team Develops Programmable RNA Tool for Cell Editing

An RNA-based editing tool that can target specific cells is reported in Nature this week. Despite advances in RNA sequencing and the accumulation of large-scale transcriptome datasets, the lack of technologies that use RNAs to observe and manipulate cell types continues to be a bottleneck in biology and medicine. In this week's report, a team led by Duke University researchers describes a programmable RNA-sensing technology for detecting specific cellular RNAs and then switching on translation of effector proteins to monitor and manipulate the cell. The approach — dubbed CellREADR, short for cell access through RNA sensing by endogenous ADAR — is deployable as a single RNA molecule and is shown to confer specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. The researchers also use CellREADR to record and control specific types of neurons in behaving mice. Since it is based on Watson-Crick base-pairing and endogenous ADAR-mediated RNA editing, CellREADR is specific to cells defined by RNA expression, easy to build and use, scalable for targeting all cells with known RNA expression in any tissue, and generalizable to most animals and humans, the researchers write. It is also programmable to achieve intersectional targeting of cells defined by expression of two or more RNAs, as well as multiplexed targeting and manipulation of several cell types in the same tissue. "Synergizing with genome and transcriptome engineering technologies, CellREADR will facilitate research towards elucidating the principles of biological information  flow from genotype to phenotype across cell types, and make possible a new generation of programmable cell-specific RNA medicine," they conclude.