Ganipineni Vijaya Durga Pradeep, Gutlapalli Sai Dheeraj, Danda Sumanth, Garlapati Sameer Krishna Prasad, Fabian Daniel, Okorie Ikpechukwu, Paramsothy Jananthan
Department of Internal Medicine, SRM Medical College Hospital and Research Centre, Chennai, IND.
Department of General Medicine, Andhra Medical College/King George Hospital, Visakhapatnam, IND.
Cureus. 2023 Mar 5;15(3):e35774. doi: 10.7759/cureus.35774. eCollection 2023 Mar.
Dilated cardiomyopathy (DCM) is one of the most important causes of heart failure in developed and developing countries. Currently, most medical interventions in the treatment of DCM are mainly focused on mitigating the progression of the disease and controlling the symptoms. The vast majority of patients who survive till the late stages of the disease require cardiac transplantation; this is exactly why we need novel therapeutic interventions and hopefully treatments that can reverse the clinical cardiac deterioration in patients with DCM. Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a novel therapeutic intervention with such capacity; it can help us edit the genome of patients with genetic etiology for DCM and potentially cure them permanently. This review provides an overview of studies investigating CRISPR-based gene editing in DCM, including the use of CRISPR in DCM disease models, phenotypic screening, and genotype-specific precision therapies. The review discusses the outcomes of these studies and highlights the potential benefits of CRISPR in developing novel genotype-agnostic therapeutic strategies for the genetic causes of DCM. The databases we used to extract relevant literature include PubMed, Google Scholar, and Cochrane Central. We used the Medical Subject Heading (MeSH) strategy for our literature search in PubMed and relevant search keywords for other databases. We screened all the relevant articles from inception till February 22, 2023. We retained 74 research articles after carefully reviewing each of them. We concluded that CRISPR gene editing has shown promise in developing precise and genotype-specific therapeutic strategies for DCM, but there are challenges and limitations, such as delivering CRISPR-Cas9 to human cardiomyocytes and the potential for unintended gene targeting. This study represents a turning point in our understanding of the mechanisms underlying DCM and paves the way for further investigation into the application of genomic editing for identifying novel therapeutic targets. This study can also act as a potential framework for novel therapeutic interventions in other genetic cardiovascular diseases.
扩张型心肌病(DCM)是发达国家和发展中国家心力衰竭的最重要原因之一。目前,DCM治疗中的大多数医学干预主要集中在减缓疾病进展和控制症状。绝大多数存活到疾病晚期的患者需要心脏移植;这正是我们需要新型治疗干预措施以及有望逆转DCM患者临床心脏恶化的治疗方法的原因。成簇规律间隔短回文重复序列(CRISPR)技术就是这样一种具有这种能力的新型治疗干预措施;它可以帮助我们编辑DCM遗传病因患者的基因组,并有可能永久治愈他们。本综述概述了研究基于CRISPR的基因编辑在DCM中的应用,包括CRISPR在DCM疾病模型中的应用、表型筛选和基因型特异性精准治疗。该综述讨论了这些研究的结果,并强调了CRISPR在为DCM的遗传病因开发新型无基因型治疗策略方面的潜在益处。我们用于提取相关文献的数据库包括PubMed、谷歌学术和考克兰中心。我们在PubMed中使用医学主题词(MeSH)策略进行文献检索,并在其他数据库中使用相关搜索关键词。我们筛选了从创刊到2023年2月22日所有的相关文章。在仔细审阅每一篇文章后,我们保留了74篇研究文章。我们得出结论,CRISPR基因编辑在为DCM开发精确的基因型特异性治疗策略方面已显示出前景,但存在挑战和局限性,如将CRISPR-Cas9递送至人类心肌细胞以及意外基因靶向的可能性。这项研究代表了我们对DCM潜在机制理解的一个转折点,并为进一步研究基因组编辑在识别新型治疗靶点中的应用铺平了道路。这项研究也可以作为其他遗传性心血管疾病新型治疗干预措施的潜在框架。