Engineered human Argonaute 2 for targeted C-to-U RNA base editing.

Human Argonaute 2 fused to a C-to-U deaminase achieves 1.9-fold higher targeted RNA editing in HEK293T cells compared to Cas13-based editors.

• Why it matters: Current RNA editing tools based on nonhuman proteins can cause unintended effects and pose challenges for therapeutic use, highlighting the need for human protein-based alternatives.
• What they did: Researchers engineered AGO2 as a modular RNA targeting domain fused with a C-to-U deaminase, using guide RNAs to enhance selectivity and reduce nuclease activity, and compared its performance to Cas13 editors.
• The result: ALTER demonstrated higher editing efficiency with similar or lower off-target effects and is predicted to produce fewer immunogenic peptides, supporting its potential for safer, human-compatible RNA editing applications.