The article discusses the recent advancements in genome editing technologies, particularly those based on programmable nucleases, and their potential applications in treating genetic diseases. It highlights the ability of these technologies to make precise changes in eukaryotic cell genomes, which has broadened our understanding of disease mechanisms and opened new therapeutic avenues. The authors review the current progress in developing programmable nuclease-based therapies, including gene therapy and RNA interference (RNAi), and discuss their limitations. They then delve into the mechanisms of genome editing, the different nuclease-based technologies, and the considerations for their therapeutic use. The article also addresses the challenges and future prospects of clinical translation, emphasizing the need for further research to optimize efficiency, specificity, and safety. Examples of successful genome editing therapeutic strategies, both ex vivo and in vivo, are provided, along with a discussion on the importance of increasing editing efficiency, improving nuclease specificity, and optimizing delivery methods. The authors conclude by highlighting the exciting potential of genome editing in treating a wide range of diseases, but also the need for strategic planning and regulatory processes to ensure its safe and effective clinical application.The article discusses the recent advancements in genome editing technologies, particularly those based on programmable nucleases, and their potential applications in treating genetic diseases. It highlights the ability of these technologies to make precise changes in eukaryotic cell genomes, which has broadened our understanding of disease mechanisms and opened new therapeutic avenues. The authors review the current progress in developing programmable nuclease-based therapies, including gene therapy and RNA interference (RNAi), and discuss their limitations. They then delve into the mechanisms of genome editing, the different nuclease-based technologies, and the considerations for their therapeutic use. The article also addresses the challenges and future prospects of clinical translation, emphasizing the need for further research to optimize efficiency, specificity, and safety. Examples of successful genome editing therapeutic strategies, both ex vivo and in vivo, are provided, along with a discussion on the importance of increasing editing efficiency, improving nuclease specificity, and optimizing delivery methods. The authors conclude by highlighting the exciting potential of genome editing in treating a wide range of diseases, but also the need for strategic planning and regulatory processes to ensure its safe and effective clinical application.