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Nucleotide metabolism constrains prime editing in hematopoietic stem and progenitor cells

Levesque, S.; Verma, A.; Bauer, D. E.

2023-10-22 genetics
10.1101/2023.10.22.563434 bioRxiv
Show abstract

Therapeutic prime editing of hematopoietic stem and progenitor cells (HSPCs) holds great potential to remedy blood disorders. Since quiescent cells have low nucleotide levels and resist retroviral infection, we hypothesized 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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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.