Core Viewpoint - The article discusses the development of a novel circular RNA-mediated inverse prime editing system (ciPE) that significantly enhances the efficiency and precision of genome editing, presenting a promising tool for disease modeling and gene therapy [2][3][11]. Group 1: Development of ciPE System - The research team developed an inverse prime editor (iPE) system using nCas9-D10A, but it initially showed limited editing efficiency, with a maximum of 8.6% [5]. - To address the low efficiency, the team designed a circular RNA (circRNA)-mediated inverse prime editor (ciPE), leveraging the unique properties of circRNA to improve editing efficiency [6]. - The ciPE editor achieved a significant improvement in editing efficiency, ranging from 0.1% to 24.7% [7]. Group 2: Enhancements with Rep-X - The introduction of a modified 3'→5' helicase, Rep-X, as a co-factor further increased the reverse editing efficiency to between 2.7% and 55.4% [7]. - The Rep-X assisted ciPE system was compared with existing prime editing systems, showing several-fold to over a hundred-fold improvements in editing efficiency at specific sites [10]. Group 3: Applications and Advantages - The ciPE system demonstrated reverse gene editing efficiencies of 13.3% for the BRCA1 gene and 9.5% for the RPE65 gene, outperforming PAMless PE and TwinPE systems [10]. - The study confirmed that the Rep-X assisted ciPE system has a higher editing purity compared to PAMless PE and TwinPE systems, indicating greater precision and safety in gene editing applications [11].