Chen Yan, Zhao Hongliang, Tan Zhijun, Zhang Cuiping, Fu Xiaobing
Pharmazie. 2015 Mar;70(3):147-54.
MicroRNAs are endogenous non-coding small RNAs that repress expression of a broad array of target genes. Research into the role and underlying molecular events of microRNAs in disease processes and the potential of microRNAs as drug targets has expanded rapidly. Significant advances have been made in identifying the associations of microRNAs with cancers, viral infections, immune diseases, cardiovascular diseases, wound healing, biological development and other areas of medicine. However, because of intense competition and financial risks, there is a series of stringent criteria and conditions that must be met before microRNA-based therapeutics could be pursued as new drug candidates. In this review, we specifically emphasized the obstacles for bench-based microRNA to the bedside, including common barriers in basic research, application limitations while moving to the clinic at the aspects of vector delivery, off-target effects, toxicity mediation, immunological activation and dosage determination, which should be overcome before microRNA-based therapeutics take their place in the clinic.
微小RNA是内源性非编码小RNA，可抑制多种靶基因的表达。对微小RNA在疾病过程中的作用及潜在分子事件，以及微小RNA作为药物靶点的潜力的研究发展迅速。在确定微小RNA与癌症、病毒感染、免疫疾病、心血管疾病、伤口愈合、生物发育及其他医学领域的关联方面已取得重大进展。然而，由于竞争激烈和存在财务风险，在将基于微小RNA的疗法作为新药候选药物进行研发之前，必须满足一系列严格的标准和条件。在本综述中，我们特别强调了从实验室研究的微小RNA到临床应用所面临的障碍，包括基础研究中的常见障碍，以及在向临床转化过程中在载体递送、脱靶效应、毒性介导、免疫激活和剂量确定等方面的应用限制，在基于微小RNA的疗法在临床中占据一席之地之前，这些障碍都应被克服。
