A recent study published in Nature Biotechnology has raised significant concerns regarding the use of DNA-PKcs inhibitors, specifically AZD7648, in genome editing applications. While these inhibitors have been employed to enhance homology-directed repair (HDR) efficiency, the research indicates that AZD7648 can induce substantial genomic alterations, including kilobase to megabase-scale deletions, chromosome arm loss, and translocations across various human cell types.
The study’s findings underscore the importance of thoroughly evaluating the genomic consequences of using DNA-PKcs inhibitors in therapeutic genome editing. The observed large-scale genomic alterations could have significant implications for the safety and efficacy of gene therapies that rely on these inhibitors to improve HDR efficiency.
These results highlight the need for caution and comprehensive assessment when considering the use of DNA-PKcs inhibitors like AZD7648 in clinical settings. Further research is essential to understand the mechanisms underlying these genomic alterations and to develop strategies that mitigate such risks, ensuring the safe application of genome editing technologies in medicine.