PolQi1 is a selective inhibitor targeting the structure domain of DNA polymerase Polθ [1]. PolQi1 can target DNA repair pathways to promote homology-directed repair (HDR) by regulating DNA polymerase Polθ[2]. The combination of PolQi1 and AZD7648 can augment the integration efficiency and editing accuracy mediated by HDR, and reduce off-target mutations and translocations[3]. PolQi1 has been widely used to upgrade the accuracy of various genome engineering editing systems and to reduce the off-target editing effects of active nuclease systems [4].
References:
[1] Mentani A, Maresca M, Shiriaeva A. Prime editing: Mechanistic insights and DNA repair modulation[J]. Cells, 2025, 14(4): 277.
[2] Haider S, Mussolino C. Fine-tuning homology-directed repair (HDR) for precision genome editing: current strategies and future directions[J]. International Journal of Molecular Sciences, 2025, 26(9): 4067.
[3] Wimberger S, Akrap N, Firth M, et al. Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing[J]. Nature communications, 2023, 14(1): 4761.
[4] Dacquay L C, Antoniou P, Mentani A, et al. Dual inhibition of DNA-PK and Polϴ boosts precision of diverse prime editing systems[J]. Nature Communications, 2025, 16(1): 4290.