Engineered human Argonaute 2 enables targeted C-to-U RNA base editing
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Researchers have built ALTER, a C-to-U RNA base editor, by fusing human AGO2 with APOBEC3A and designing guide sequences that induce RNA looping. Tested in an EGFP Y66H reporter system and at endogenous targets including PPIB, SMARCA4, ACTB and TYMS, the ALTER-4 variant showed editing activity comparable to or higher than the dCas13-derived editors RESCUE-S and CURE-N. Lowering the transfection dose reduced off-target editing about 25-fold, pointing to a route toward more precise RNA editing. The work, published in Nature Biotechnology, establishes a Cas13-free platform for programmable RNA modification. Questions still open include how the approach performs in vivo and whether the off-target reduction holds across cell types and clinically relevant targets.
Written by a model from the reports · updated 3 hours ago
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- NaturePickEngineered human Argonaute 2 for targeted C-to-U RNA base editing
A research team fused human AGO2 with APOBEC3A and designed guide sequences that induce RNA circularization, creating the C-to-U RNA base editor ALTER. In the EGFP Y66H reporter system and at endogenous targets including PPIB, SMARCA4, ACTB and TYMS, ALTER-4 showed editing activity comparable to or higher than the dCas13-derived RESCUE-S and CURE-S; lowering transfection dose reduced off-target editing about 25-fold.
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