Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385810274> ?p ?o ?g. }
- W4385810274 abstract "Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing." @default.
- W4385810274 created "2023-08-15" @default.
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- W4385810274 date "2023-08-14" @default.
- W4385810274 modified "2023-09-30" @default.
- W4385810274 title "Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing" @default.
- W4385810274 cites W1543815058 @default.
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- W4385810274 cites W1970827792 @default.
- W4385810274 cites W1979240756 @default.
- W4385810274 cites W1980053292 @default.
- W4385810274 cites W1989924028 @default.
- W4385810274 cites W2003797386 @default.
- W4385810274 cites W2007321086 @default.
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- W4385810274 cites W2020991778 @default.
- W4385810274 cites W2027379868 @default.
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- W4385810274 cites W2057902837 @default.
- W4385810274 cites W2071156666 @default.
- W4385810274 cites W2072299899 @default.
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- W4385810274 cites W2099391093 @default.
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- W4385810274 cites W2146204567 @default.
- W4385810274 cites W2156709395 @default.
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- W4385810274 cites W2163090183 @default.
- W4385810274 cites W2166401696 @default.
- W4385810274 cites W2168396953 @default.
- W4385810274 cites W2206983740 @default.
- W4385810274 cites W2255497367 @default.
- W4385810274 cites W2285408387 @default.
- W4385810274 cites W2330335659 @default.
- W4385810274 cites W2336346625 @default.
- W4385810274 cites W2336957559 @default.
- W4385810274 cites W2418150343 @default.
- W4385810274 cites W2476261929 @default.
- W4385810274 cites W2484964216 @default.
- W4385810274 cites W2503342171 @default.
- W4385810274 cites W2509775353 @default.
- W4385810274 cites W2547418311 @default.
- W4385810274 cites W2550079706 @default.
- W4385810274 cites W2550897879 @default.
- W4385810274 cites W2562446577 @default.
- W4385810274 cites W2589417329 @default.
- W4385810274 cites W2605113678 @default.
- W4385810274 cites W2606996398 @default.
- W4385810274 cites W2616802735 @default.
- W4385810274 cites W2648902637 @default.
- W4385810274 cites W2754886024 @default.
- W4385810274 cites W2765241881 @default.
- W4385810274 cites W2767848910 @default.
- W4385810274 cites W2768392728 @default.
- W4385810274 cites W2774316419 @default.
- W4385810274 cites W2789843538 @default.
- W4385810274 cites W2804348137 @default.
- W4385810274 cites W2804432738 @default.
- W4385810274 cites W2809529383 @default.
- W4385810274 cites W2883625359 @default.
- W4385810274 cites W2884957258 @default.
- W4385810274 cites W2899807648 @default.
- W4385810274 cites W2902555008 @default.
- W4385810274 cites W2915459742 @default.
- W4385810274 cites W2937469308 @default.
- W4385810274 cites W2945177467 @default.
- W4385810274 cites W2950124537 @default.
- W4385810274 cites W2950564381 @default.
- W4385810274 cites W2955620588 @default.
- W4385810274 cites W2968784210 @default.