Convenience-sized RNA editing

Good news!

"Last year, researchers at ... discovered and characterized Cas7-11, the first CRISPR enzyme capable of making precise, guided cuts to strands of RNA without harming cells in the process. Now, working with collaborators at the University of Tokyo, the same team has revealed that Cas7-11 can be shrunk to a more compact version, making it an even more viable option for editing the RNA inside living cells. The new, compact Cas7-11 was described May 27 in the journal Cell along with a detailed structural analysis of the original enzyme. ...
But CRISPR-Cas9 only works to alter DNA, and for some research and clinical purposes, editing RNA is more effective or useful. ...
The discovery of Cas7-11 opened the doors to a more precise form of RNA editing, analogous to the Cas9 enzyme for DNA. However, the massive Cas7-11 protein was too big to fit inside a single viral vector ..."

From the abstract:

"The type III-E CRISPR-Cas effector Cas7-11, with dual RNase activities for precursor CRISPR RNA (pre-crRNA) processing and crRNA-guided target RNA cleavage, is a new platform for bacterial and mammalian RNA targeting. We report the 2.5-Å resolution cryoelectron microscopy structure of Cas7-11 in complex with a crRNA and its target RNA. Cas7-11 adopts a modular architecture comprising seven domains (Cas7.1–Cas7.4, Cas11, INS, and CTE) and four interdomain linkers. The crRNA 5′ tag is recognized and processed by Cas7.1, whereas the crRNA spacer hybridizes with the target RNA. Consistent with our biochemical data, the catalytic residues for programmable cleavage in Cas7.2 and Cas7.3 neighbor the scissile phosphates before the flipped-out fourth and tenth nucleotides in the target RNA, respectively. Using structural insights, we rationally engineered a compact Cas7-11 variant (Cas7-11S) for single-vector AAV packaging for transcript knockdown in human cells, enabling in vivo Cas7-11 applications."

Convenience-sized RNA editing | MIT News | Massachusetts Institute of Technology MIT neuroscientists expand CRISPR toolkit with new, compact Cas7-11 enzyme.

Structure and engineering of the type III-E CRISPR-Cas7-11 effector complex (no public access)