Matches in SemOpenAlex for { <https://semopenalex.org/work/W4311595561> ?p ?o ?g. }
- W4311595561 abstract "ABSTRACT Genome editing tools, especially CRISPR/Cas9-based strategies, have transformed biomedical research and opened opportunities for developing curative treatments for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of undesired mutations represent major limitations for genome editing applications. Both issues arise from the interplay between the main DNA Double-Strand Break (DSB) repair pathways, Homology-Directed Repair (HDR), Non-Homologous End Joining (NHEJ), and Microhomology-Mediated End Joining (MMEJ). To improve efficiencies of targeted CRISPR-Cas9 genome editing, we screened a large compound library. This led to the discovery of AZD7648, a DNA-dependent protein kinase (DNA-PK) inhibitor and potent enhancer of CRISPR-Cas9-mediated integration. We demonstrated that AZD7648 increased HDR and decreased mutagenic NHEJ repair, thus resulting in improved performance of precise gene editing. Furthermore, we observed additional improvement of integration efficiency by impairing MMEJ repair through DNA polymerase ⊖ (Pol⊖) inhibition. Combined treatment with AZD7648 and Pol⊖ inhibitors (which we named 2iHDR) substantially increased precision of templated insertions, with efficiencies of up to 80%, and nearly no formation of undesired Insertion-Deletions (InDels). Importantly, 2iHDR also decreased Cas9-associated off-target activity, dramatically improving the performance and fidelity of CRISPR-Cas9 gene editing." @default.
- W4311595561 created "2022-12-27" @default.
- W4311595561 creator A5003944945 @default.
- W4311595561 creator A5006358230 @default.
- W4311595561 creator A5010497925 @default.
- W4311595561 creator A5013153524 @default.
- W4311595561 creator A5015089998 @default.
- W4311595561 creator A5017408177 @default.
- W4311595561 creator A5025981553 @default.
- W4311595561 creator A5026768700 @default.
- W4311595561 creator A5028725423 @default.
- W4311595561 creator A5028743716 @default.
- W4311595561 creator A5036018926 @default.
- W4311595561 creator A5036932336 @default.
- W4311595561 creator A5037908617 @default.
- W4311595561 creator A5046921613 @default.
- W4311595561 creator A5050012419 @default.
- W4311595561 creator A5058204125 @default.
- W4311595561 creator A5058873811 @default.
- W4311595561 creator A5063281864 @default.
- W4311595561 creator A5064891550 @default.
- W4311595561 creator A5066204608 @default.
- W4311595561 creator A5075463006 @default.
- W4311595561 creator A5076975589 @default.
- W4311595561 creator A5079799883 @default.
- W4311595561 creator A5080177447 @default.
- W4311595561 creator A5082026543 @default.
- W4311595561 creator A5082473547 @default.
- W4311595561 creator A5083333226 @default.
- W4311595561 creator A5077166021 @default.
- W4311595561 date "2022-12-15" @default.
- W4311595561 modified "2023-10-15" @default.
- W4311595561 title "Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing" @default.
- W4311595561 cites W1543815058 @default.
- W4311595561 cites W1906870688 @default.
- W4311595561 cites W1966297218 @default.
- W4311595561 cites W1970810396 @default.
- W4311595561 cites W1970827792 @default.
- W4311595561 cites W1979240756 @default.
- W4311595561 cites W1980053292 @default.
- W4311595561 cites W2003797386 @default.
- W4311595561 cites W2007321086 @default.
- W4311595561 cites W2020091112 @default.
- W4311595561 cites W2020991778 @default.
- W4311595561 cites W2027379868 @default.
- W4311595561 cites W2050480410 @default.
- W4311595561 cites W2056406429 @default.
- W4311595561 cites W2057902837 @default.
- W4311595561 cites W2071156666 @default.
- W4311595561 cites W2072299899 @default.
- W4311595561 cites W2097583984 @default.
- W4311595561 cites W2102619694 @default.
- W4311595561 cites W2146204567 @default.
- W4311595561 cites W2156709395 @default.
- W4311595561 cites W2158789637 @default.
- W4311595561 cites W2163090183 @default.
- W4311595561 cites W2166401696 @default.
- W4311595561 cites W2168396953 @default.
- W4311595561 cites W2206983740 @default.
- W4311595561 cites W2255497367 @default.
- W4311595561 cites W2330335659 @default.
- W4311595561 cites W2336346625 @default.
- W4311595561 cites W2336957559 @default.
- W4311595561 cites W2418150343 @default.
- W4311595561 cites W2484964216 @default.
- W4311595561 cites W2503342171 @default.
- W4311595561 cites W2509775353 @default.
- W4311595561 cites W2547418311 @default.
- W4311595561 cites W2550079706 @default.
- W4311595561 cites W2550897879 @default.
- W4311595561 cites W2562446577 @default.
- W4311595561 cites W2589417329 @default.
- W4311595561 cites W2605113678 @default.
- W4311595561 cites W2606996398 @default.
- W4311595561 cites W2616802735 @default.
- W4311595561 cites W2648902637 @default.
- W4311595561 cites W2754886024 @default.
- W4311595561 cites W2768392728 @default.
- W4311595561 cites W2774316419 @default.
- W4311595561 cites W2789843538 @default.
- W4311595561 cites W2804348137 @default.
- W4311595561 cites W2804432738 @default.
- W4311595561 cites W2809529383 @default.
- W4311595561 cites W2883625359 @default.
- W4311595561 cites W2884957258 @default.
- W4311595561 cites W2899807648 @default.
- W4311595561 cites W2902555008 @default.
- W4311595561 cites W2915459742 @default.
- W4311595561 cites W2937469308 @default.
- W4311595561 cites W2945177467 @default.
- W4311595561 cites W2950124537 @default.
- W4311595561 cites W2950564381 @default.
- W4311595561 cites W2953786622 @default.
- W4311595561 cites W2955620588 @default.
- W4311595561 cites W2968784210 @default.
- W4311595561 cites W2970098032 @default.
- W4311595561 cites W2977140302 @default.
- W4311595561 cites W2985561224 @default.
- W4311595561 cites W3006116138 @default.
- W4311595561 cites W3026324878 @default.