Departments of Neurosurgery (T.J.L., K.K., J.Y.Y., D.H.K., B.K.) and Anesthesiology (X.Y., H.K.E.), McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas
Departments of Neurosurgery (T.J.L., K.K., J.Y.Y., D.H.K., B.K.) and Anesthesiology (X.Y., H.K.E.), McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
Pharmacol Rev. 2020 Jul;72(3):639-667. doi: 10.1124/pr.119.019026.
Cancer and organ injury-such as that occurring in the perioperative period, including acute lung injury, myocardial infarction, and acute gut injury-are among the leading causes of death in the United States and impose a significant impact on quality of life. MicroRNAs (miRNAs) have been studied extensively during the last two decades for their role as regulators of gene expression, their translational application as diagnostic markers, and their potential as therapeutic targets for disease treatment. Despite promising preclinical outcomes implicating miRNA targets in disease treatment, only a few miRNAs have reached clinical trials. This likely relates to difficulties in the delivery of miRNA drugs to their targets to achieve efficient inhibition or overexpression. Therefore, understanding how to efficiently deliver miRNAs into diseased tissues and specific cell types in patients is critical. This review summarizes current knowledge on various approaches to deliver therapeutic miRNAs or miRNA inhibitors and highlights current progress in miRNA-based disease therapy that has reached clinical trials. Based on ongoing advances in miRNA delivery, we believe that additional therapeutic approaches to modulate miRNA function will soon enter routine medical treatment of human disease, particularly for cancer or perioperative organ injury. SIGNIFICANCE STATEMENT: MicroRNAs have been studied extensively during the last two decades in cancer and organ injury, including acute lung injury, myocardial infarction, and acute gut injury, for their regulation of gene expression, application as diagnostic markers, and therapeutic potentials. In this review, we specifically emphasize the pros and cons of different delivery approaches to modulate microRNAs, as well as the most recent exciting progress in the field of therapeutic targeting of microRNAs for disease treatment in patients.
癌症和器官损伤——如围手术期发生的急性肺损伤、心肌梗死和急性肠道损伤——是美国主要的死亡原因之一，并对生活质量造成重大影响。在过去的二十年中，microRNAs (miRNAs) 因其作为基因表达调控因子的作用、作为诊断标志物的应用以及作为疾病治疗的治疗靶点的潜力而得到广泛研究。尽管有前景的临床前结果表明 miRNA 靶点在疾病治疗中的作用，但只有少数 miRNA 进入临床试验。这可能与 miRNA 药物递送至其靶标以实现有效抑制或过表达的困难有关。因此，了解如何将 miRNAs 有效递送至患病组织和患者的特定细胞类型至关重要。本综述总结了目前关于递送治疗性 miRNAs 或 miRNA 抑制剂的各种方法的知识，并强调了已达到临床试验的基于 miRNA 的疾病治疗的最新进展。基于 miRNA 递送的持续进展，我们相信，调节 miRNA 功能的其他治疗方法将很快进入人类疾病的常规医疗，特别是在癌症或围手术期器官损伤方面。
在过去的二十年中，miRNAs 在癌症和器官损伤（包括急性肺损伤、心肌梗死和急性肠道损伤）的研究中得到了广泛的研究，因为它们可以调节基因表达、作为诊断标志物的应用以及治疗潜力。在这篇综述中，我们特别强调了调节 miRNAs 的不同递送方法的优缺点，以及在治疗性靶向 miRNAs 治疗疾病方面的最新令人兴奋的进展。
