Programmable recruitment of PCBP2 stabilizes pegRNAs to enhance prime editing and large-fragment rewriting

Prime editing (PE) enables versatile and precise genome modifications without double-strand breaks (DSBs), yet its efficiency is frequently limited by the instability of prime editing guide RNAs (pegRNAs) 3 extensions. Here, we systematically screened human sequence-specific RNA-binding proteins (RBPs) as PE fusion partners alongside cognate motif-engineered pegRNAs, identifing the poly(C)-binding protein 2 (PCBP2) as a potent enhancer of PE activity.