Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
Deutsches Zentrum für Herz- und Kreislaufforschung (DZHK), Munich Heart Alliance, Munich, Germany.
Adv Exp Med Biol. 2023;1396:139-156. doi: 10.1007/978-981-19-5642-3_10.
Despite successive advancement of genome editing technology with zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the recent breakthrough in the field has been related to clustered regularly interspaced short palindromic repeats/associated proteins (CRISPR/Cas). The high efficiency and convenience of CRIPSR/Cas systems dramatically accelerate pre- and clinical experimentations of dyslipidemia and atherosclerosis. In this chapter, we review the latest state of genome editing in translational research of dyslipidemia and atherosclerosis. We highlight recent progress in therapeutic development for familial dyslipidemia by genome editing. We point to the challenges in maximizing efficacy and minimizing safety issues related to the once-and-done therapy focusing on CRISPR/Cas systems. We give an outlook on the potential gene targets prioritized by large-scale genetic studies of cardiovascular diseases and genome editing in precision medicine of dyslipidemia and atherosclerosis.
尽管锌指核酸酶（ZFNs）和转录激活因子样效应核酸酶（TALENs）的基因组编辑技术不断取得进展，但该领域的最新突破与成簇规律间隔短回文重复序列/相关蛋白（CRISPR/Cas）有关。CRISPR/Cas 系统的高效率和便利性极大地加速了血脂异常和动脉粥样硬化的临床前和临床试验。在这一章中，我们综述了基因组编辑在血脂异常和动脉粥样硬化转化研究中的最新进展。我们强调了基因组编辑在治疗家族性血脂异常方面的最新进展。我们指出，在聚焦于 CRISPR/Cas 系统的一次性治疗中，如何最大限度地提高疗效和降低安全性问题方面存在挑战。我们展望了大规模心血管疾病遗传学研究和血脂异常及动脉粥样硬化精准医学中基因组编辑优先考虑的潜在基因靶点。
