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Updated: Jun 25, 2025

CRISPR/Cas9 Gene Editing of Hematopoietic Stem and Progenitor Cells for Gene Therapy Applications
Published on: August 9, 2022
Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism
Sébastien Levesque1,2,3,4,5, Andrea Cosentino1,2,5,6, Archana Verma1,2,3,4,5
1Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
Abstract:
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.
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