Genome editing has the potential to treat an extensive range of incurable monogenic and complex diseases. In particular, advances in sequence-specific nuclease technologies have dramatically accelerated the development of therapeutic genome editing strategies that are based on either the knockout of disease-causing genes or the repair of endogenous mutated genes. These technologies are progressing into human clinical trials. However, challenges remain before the therapeutic potential of genome editing can be fully realized. Delivery technologies that have serendipitously been developed over the past couple decades in the protein and nucleic acid delivery fields have been crucial to genome editing success to date, including adeno-associated viral and lentiviral vectors for gene therapy and lipid nanoparticle and other non-viral vectors for nucleic acid and protein delivery. However, the efficiency and tissue targeting capabilities of these vehicles must be further improved. In addition, the genome editing enzymes themselves need to be optimized, and challenges regarding their editing efficiency, specificity and immunogenicity must be addressed. Emerging protein engineering and synthetic chemistry approaches can offer solutions and enable the development of safe and efficacious clinical genome editing.

基因组编辑有可能治疗广泛的无法治愈的单基因和复杂疾病。特别是，序列特异性核酸酶技术的进步极大地加速了基于致病基因敲除或内源性突变基因修复的治疗性基因组编辑策略的开发。这些技术正在进入人体临床试验。然而，在完全实现基因组编辑的治疗潜力之前，挑战仍然存在。过去几十年在蛋白质和核酸递送领域偶然开发的递送技术对于迄今为止基因组编辑的成功至关重要，包括用于基因治疗的腺相关病毒和慢病毒载体以及用于核酸和蛋白质递送的脂质纳米颗粒和其他非病毒载体。然而，这些车辆的效率和组织靶向能力必须进一步提高。此外，基因组编辑酶本身需要优化，必须解决其编辑效率、特异性和免疫原性方面的挑战。新兴的蛋白质工程和合成化学方法可以提供解决方案，并能够开发安全有效的临床基因组编辑。必须解决特异性和免疫原性问题。新兴的蛋白质工程和合成化学方法可以提供解决方案，并能够开发安全有效的临床基因组编辑。必须解决特异性和免疫原性问题。新兴的蛋白质工程和合成化学方法可以提供解决方案，并能够开发安全有效的临床基因组编辑。