Prime Editing in Dividing and Quiescent Cells

Prime editing is a method of genome editing based on reverse transcription. Recent results have shown its elevated efficiency in dividing cells, which raises some questions regarding the mechanism of this effect, because prime editing does not employ homology-driven repair. This mini review aims to identify the reason for this phenomenon and find a possible solution to the problems that it poses. In dividing cells, prime editing takes advantage of high levels of dNTPs and active endonuclease and ligase machinery, such as FEN1 endonuclease and LIG1 ligase, but DNA mismatch repair, which is closely associated with replication, works against prime editing. Prime editing is a method which relies on retroviral reverse transcription, so mechanisms of intrinsic anti-retroviral defense should also work against editing. One of the factors which drastically reduce the efficiency of reverse translation is SAMHD1, which maintains low levels of dNTPs in non-dividing cells. Recent works aimed at the mitigation of SAMHD1 function demonstrated a significant increase in prime editing efficiency.