Gallicano G Ian, Fu Jiayu, Mahapatra Samiksha, Sharma Michael V R, Dillon Conor, Deng Claire, Zahid Maliha
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 3900 Reservoir Rd, Washington, DC 20057, USA.
Celprogen, Torrance, CA 90503, USA.
Pharmaceuticals (Basel). 2022 Jul 15;15(7):871. doi: 10.3390/ph15070871.
Causes and treatments for heart failure (HF) have been investigated for over a century culminating in data that have led to numerous pharmacological and surgical therapies. Unfortunately, to date, even with the most current treatments, HF remains a progressive disease with no therapies targeting the cardiomyocytes directly. Technological advances within the past two to three years have brought about new paradigms for treating many diseases that previously had been extremely difficult to resolve. One of these new paradigms has been a shift from pharmacological agents to antisense technology (e.g., microRNAs) to target the molecular underpinnings of pathological processes leading to disease onset. Although this paradigm shift may have been postulated over a decade ago, only within the past few years has it become feasible. Here, we show that miRNA106a targets genes that, when misregulated, have been shown to cause hypertrophy and eventual HF. The addition of miRNA106a suppresses misexpressed HF genes and reverses hypertrophy. Most importantly, using a cardiac targeting peptide reversibly linked to miRNA106a, we show delivery is specific to cardiomyocytes.
心力衰竭（HF）的病因和治疗方法已经研究了一个多世纪，最终得出的数据催生了众多药物和手术治疗方法。不幸的是，迄今为止，即使采用最新的治疗方法，HF仍然是一种进行性疾病，尚无直接针对心肌细胞的治疗方法。过去两到三年的技术进步为治疗许多以前极难解决的疾病带来了新的范例。其中一个新范例是从药物制剂转向反义技术（例如，微小RNA），以针对导致疾病发作的病理过程的分子基础。尽管这种范式转变可能在十多年前就已被提出，但直到最近几年才变得可行。在这里，我们表明miRNA106a靶向那些调控异常时会导致肥大并最终引发HF的基因。添加miRNA106a可抑制HF基因的错误表达并逆转肥大。最重要的是，使用与miRNA106a可逆连接的心脏靶向肽，我们证明了这种递送对心肌细胞具有特异性。
