articleNature BiotechnologySep 7, 2023HYBRID OA

Genotoxic effects of base and prime editing in human hematopoietic stem cells

MFMartina FiumaraSFSamuele FerrariAOAttya OmerSBStefano BerettaLALuisa Albano

Vita-Salute San Raffaele University · The San Raffaele Telethon Institute for Gene Therapy · +4 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Base and prime editors (BEs and PEs) may provide more precise genetic engineering than nuclease-based approaches because they bypass the dependence on DNA double-strand breaks. However, little is known about their cellular responses and genotoxicity. Here, we compared state-of-the-art BEs and PEs and Cas9 in human hematopoietic stem and progenitor cells with respect to editing efficiency, cytotoxicity, transcriptomic changes and on-target and genome-wide genotoxicity. BEs and PEs induced detrimental transcriptional responses that reduced editing efficiency and hematopoietic repopulation in xenotransplants and also generated DNA double-strand breaks and genotoxic byproducts, including deletions and…

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212
total citations
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31.66
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100%
References
59
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Authors

16

Topics & keywords

Topics
Keywords
  • Haematopoiesis
  • Stem cell
  • Prime (order theory)
  • Base (topology)
  • Biology
  • Computational biology
  • Genetics
  • Mathematics
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