Figure 5.

Applications of type VI CRISPR‐Cas systems in transcriptome engineering. Type VI CRISPR‐Cas systems can be used to manipulate cellular RNA in numerous ways both for basic research and therapeutics. While catalytically active Cas13 variants can be applied in targeted RNA knockdown, the fact that inactive Cas13‐gRNA complex retains specific RNA‐binding properties allows targeted disruption of RNA binding by other proteins in applications such as regulation of alternative splicing. Fusing RNA‐modifying enzymes to Cas13 effectors further expands transcriptome manipulation methods to site‐directed nucleobase editing, epitranscriptome modulation (e.g., regulation of m⁶A modifications) and labeling of RNA‐interacting proteins. Other RNA manipulation methods such as translational activation/repression and localization may be achieved by linking inactive Cas13 effectors to certain signal peptides. Abbreviations: ADAR, adenosine deaminase acting on RNA; APOBEC, apolipoprotein B mRNA editing enzyme, catalytic polypeptide‐like; PUS, pseudouridine synthase.