Gene editing innovations and their applications in cardiomyopathy research

Abstract

ABSTRACT 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.