Therapeutic prime editing of hematopoietic stem and progenitor cells (HSPCs) holds great potential to remedy blood disorders. Quiescent cells have low nucleotide levels and resist retroviral infection, and it is possible that nucleotide metabolism could limit reverse transcription-mediated prime editing in HSPCs. We demonstrate that deoxynucleoside supplementation and Vpx-mediated degradation of SAMHD1 improve prime editing efficiency in HSPCs, especially when coupled with editing approaches that evade mismatch repair.

中文翻译：

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通过调节核苷酸代谢增强造血干细胞和祖细胞的初等编辑

造血干细胞和祖细胞 (HSPC) 的治疗性初始编辑在治疗血液疾病方面具有巨大潜力。静止细胞的核苷酸水平较低，可以抵抗逆转录病毒感染，并且核苷酸代谢可能会限制 HSPC 中逆转录介导的引物编辑。我们证明，脱氧核苷补充和 Vpx 介导的 SAMHD1 降解可提高 HSPC 中的主要编辑效率，特别是与逃避错配修复的编辑方法结合使用时。