Science Daily  September 27, 2023
The CRISPR-Cas13 ribonucleases have been widely applied for RNA knockdown and transcriptional modulation owing to their high programmability and specificity. However, the large size of Cas13 effectors and their non-specific RNA cleavage upon target activation limit the adeno-associated virus-based delivery of Cas13 systems for therapeutic applications. Researchers at Rice University descried detailed biochemical and structural characterizations of a compact Cas13 (Cas13bt3) suitable for adeno-associated virus delivery. Distinct from many other Cas13 systems, Cas13bt3 cleaves the target and other nonspecific RNA at internal “UC” sites and was activated in a target length-dependent manner. The cryo-electron microscope structure of Cas13bt3 in a fully active state illustrated the structural basis of Cas13bt3 activation. Guided by the structure, they obtained engineered Cas13bt3 variants with minimal off-target cleavage yet maintained target cleavage activities. According to the researchers their biochemical and structural data illustrated a distinct mechanism for Cas13bt3 activation and guided the engineering of Cas13bt3 applications… read more. Open Access TECHNICAL ARTICLE
Model for Cas13bt3 catalyzed crRNA-guided RNA cleavage. Credit: Nature Communications volume 14, Article number: 5845 (2023)Â