Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center, 3584CT Utrecht, The Netherlands.
Department of Cardiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
Dis Model Mech. 2023 May 1;16(5). doi: 10.1242/dmm.050088. Epub 2023 May 24.
Cardiomyopathies are among the major triggers of heart failure, but their clinical and genetic complexity have hampered our understanding of these disorders and delayed the development of effective treatments. Alongside the recent identification of multiple cardiomyopathy-associated genetic variants, advances in genome editing are providing new opportunities for cardiac disease modeling and therapeutic intervention, both in vitro and in vivo. Two recent innovations in this field, prime and base editors, have improved editing precision and efficiency, and are opening up new possibilities for gene editing of postmitotic tissues, such as the heart. Here, we review recent advances in prime and base editors, the methods to optimize their delivery and targeting efficiency, their strengths and limitations, and the challenges that remain to be addressed to improve the application of these tools to the heart and their translation to the clinic.
心肌病是心力衰竭的主要诱因之一,但它们在临床和遗传方面的复杂性阻碍了我们对这些疾病的理解,并延缓了有效治疗方法的发展。除了最近发现多种与心肌病相关的遗传变异外,基因组编辑技术的进步也为心脏疾病的体外和体内建模和治疗干预提供了新的机会。该领域的两项最新创新——Prime 和 Base 编辑器提高了编辑精度和效率,并为有丝分裂后组织(如心脏)的基因编辑开辟了新的可能性。在这里,我们回顾了 Prime 和 Base 编辑器的最新进展,优化其递送和靶向效率的方法,它们的优缺点,以及仍然需要解决的挑战,以提高这些工具在心脏中的应用和向临床的转化。