Public Release: 25-Oct-2017
American Association for the Advancement of Science
A new version of the gene editing tool CRISPR can target and edit RNA, scientists report, yielding several advantages over its DNA-editing counterpart. For example, the ability to edit RNA allows scientists to correct mutations in different time windows – including during key developmental periods. And, correcting RNA instead of DNA in such cases would be sufficient, say the authors, alleviating DNA editing-associated ethical concerns. To design their RNA editing tool, David Cox, Feng Zhang and colleagues closely characterized new subfamilies of the Cas protein (a nucleic acid-cutting enzyme). The scientists uncovered an active version of Cas13, dubbed Cas13b. They designed a version of Cas13b and fused it with the ADAR protein (an RNA adenosine deaminase that can convert adenosines to inosines), resulting in a platform they call REPAIR. Using REPAIR, Cox et al. achieved targeted editing of specific RNA bases at efficiencies routinely ranging from 20 to 40% – and up to 89%, in some instances. An engineered variant, REPAIRv2, demonstrated a greater than 900-fold increase in specificity. To further test their setup, the researchers used REPAIRv2 to modify full-length stretches of RNA sequences containing known mutations. The authors say Cas13b can correct multiple mutations, which alone might not alter disease risk, but combined might have additive effects and disease-modifying potential. Extension of their design (such as combining promising mutations) could further increase the efficiency and specificity of the system, they say. The advance may open a completely new avenue in both research and clinics.