Designed human Argonaute 2 protein for precise RNA editing from C to U

Human Argonaute 2 (AGO2) achieves an average of 1.9-fold higher C-to-U editing on mRNA targets in HEK293T cells compared to Cas13 editors.

• Replacing nonhuman proteins with human proteins may reduce unintended effects on human cells.
• AGO2 can be repurposed as a modular domain for targeting RNA.
• A fusion of AGO2 with a C-to-U deaminase enables targeted editing of RNA.
• Transcriptome-wide RNA sequencing indicates similar or lower off-target editing levels compared to Cas13-based editors.
• Machine learning models predict that ALTER could generate fewer immunogenic peptides.

Simplified