۱- Introduction

۲- Potential target diseases of genome editing in the cardiovascular field

۳- Molecular mechanisms and strategies of genome editing to treat or prevent diseases

۴- Current hurdles for therapeutic genome editing

۵- Conclusions

References

Abstract

During the past decade, developments in genome editing technology have fundamentally transformed biomedical research. In particular, the CRISPR/Cas9 system has been extensively applied because of its simplicity and ability to alter genomic sequences within living organisms, and an ever increasing number of CRISPR/Cas9-based molecular tools are being developed for a wide variety of applications. While genome editing tools have been used for many aspects of biological research, they also have enormous potential to be used for genome editing therapy to treat a broad range of diseases. For some hematopoietic diseases, clinical trials of therapeutic genome editing with CRISPR/Cas9 are already starting phase I. In the cardiovascular field, genome editing tools have been utilized to understand the mechanisms of diseases such as cardiomyopathy, arrythmia, and lipid metabolism, which now open the door to therapeutic genome editing. Currently, therapeutic genome editing in the cardiovascular field is centered on liver-targeting strategies to reduce cardiovascular risks. Targeting the heart is more challenging. In this review, we discuss the potential applications, recent advances, and current limitations of therapeutic genome editing in the cardiovascular field.

Introduction

The development of genome editing technology was one of the biggest advances in biology in the last decade, and it has revolutionized biomedical research [1-4]. Compared to methods using conventional homologous recombination, which also can modify genomic sequences and are commonly used to generate genetic models, the new genome editing tools have made it much easier and faster to alter genomic DNA sequences within the genome of living organisms. Basically, the genome editing tools harness the endogenous repair process of DNA double-strand breaks (DSBs) generated by programmable nucleases such as zinc finger nucleases (ZFNs) [5], transcription activator-like effector nucleases (TALENs) [6, 7], and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) [2-4] nucleases. In particular, the key initial technological breakthrough was the application of CRISPR/Cas9 system, which was originally discovered as a part of the immune system within bacteria, to eukaryotic genome editing [8]. Because of their simplicity and efficiency, CRISPR/Cas9 genome editing tools have been widely adopted in various scientific fields.