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. 2025 Apr;43(4):534-538.
doi: 10.1038/s41587-024-02266-4. Epub 2024 May 28.

Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism

Sébastien Levesque  1   2   3   4   5 , Andrea Cosentino  1   2   5   6 , Archana Verma  1   2   3   4   5 , Pietro Genovese  1   2   3   4   5 , Daniel E Bauer  7   8   9   10   11
Affiliations

Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism

Sébastien Levesque et al. Nat Biotechnol. 2025 Apr.

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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Conflict of interest statement

Competing interests: S.L. and D.E.B. have filed a provisional patent application related to this work. All other authors have no competing interests.

References

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