The recently reported prime editor (PE) can produce all types of base substitution, insertion and deletion, greatly expanding the scope of genome editing. However, improving the editing efficiency and precision of PE represents a major challenge. Here, we report an approach termed the homologous 3′ extension mediated prime editor (HOPE). HOPE uses paired prime editing guide RNAs (pegRNAs) encoding the same edits in both sense and antisense DNA strands to achieve high editing efficiency in human embryonic kidney 293T cells as well as mismatch repair-deficient human colorectal carcinoma 116 cells. In addition, we found that HOPE shows greatly improved product purity compared to the original PE3 system. We envision that this enhanced tool could broaden both fundamental research and therapeutic applications of prime editing.

最近报道的prime editor（PE）可以产生所有类型的碱基替换、插入和删除，极大地扩展了基因组编辑的范围。然而，提高PE的编辑效率和精度是一个重大挑战。在这里，我们报告了一种称为同源 3' 延伸介导的初等编辑器 (HOPE) 的方法。 HOPE 使用配对引物编辑向导 RNA (pegRNA) 在正义和反义 DNA 链中编码相同的编辑，以在人胚胎肾 293T 细胞以及错配修复缺陷的人结直肠癌 116 细胞中实现高编辑效率。此外，我们发现与原始 PE3 系统相比，HOPE 的产品纯度大大提高。我们预计，这种增强的工具可以拓宽prime编辑的基础研究和治疗应用。