Turning IscB and Cas9 Proteins into Tools That Edit RNA Using Guide RNA

An ultracompact RNA-editing platform, R-IscB, demonstrates comparable or higher activity than Cas13 without causing cytotoxicity.

• R-IscB is engineered from IscB, the evolutionary ancestor of Cas9, and shows no collateral RNA cleavage activity.
• The platform can efficiently alter splicing outcomes in human cells and correct mutations at the mRNA level through trans-splicing.
• R-IscB facilitates A-to-I editing on mRNA when combined with adenosine deaminase acting on RNA 2 (ADAR2).
• The same engineering approach allows some Cas9 variants to function as RNA-targeting tools.

Simplified