CRISPR Platform Brings C-to-U Base Editing to RNA

A new tool in the CRISPR toolbox doubles the number of single-base RNA edits on researchers wish lists. The tool aptly named RNA Editing for Specific C-to-U Exchange (RESCUE) can be programmed to convert targeted cytosine bases into uridine bases, complementing existing RNA base editors, which convert targeted adenine bases into inosine bases. RESCUE, its creators declare, is a particularly welcome development because many of the transcript modifications within RESCUE’s purview correspond to protein modifications relevant to cell signaling and cancer-linked pathways. For example, RESCUE enables modulation of more posttranslational modifications, such as phosphorylation, glycosylation, and methylation, as well as expanded targeting of common catalytic residues, disease mutations, and protective alleles. RESCUE was developed by a team of scientists led by Feng Zhang, PhD, an investigator at the McGovern Institute and a core member of the Broad Institute of MIT and Harvard. Zhang and colleagues made use of a deactivated Cas13 to guide RESCUE to targeted cytosine bases on RNA transcripts. Also, the scientists used a novel, evolved, programmable enzyme to convert unwanted cytosine into uridine—thereby directing a change in the RNA instructions.