Gibson N W
NW Gibson, Regulus Therapeutics Inc, 3545 John Hopkins Court, San Diego, CA 92121-1121, USA. Email
J R Coll Physicians Edinb. 2014;44(3):196-200. doi: 10.4997/JRCPE.2014.302.
Targeting of microRNAs that are overexpressed or replacement of microRNAs whose expression is lost are two distinct and novel approaches to treat disease(s) driven by microRNA dysregulation. This can be achieved by chemical modification of either a single stranded oligonucleotide called an antimiR or a double stranded nucleic acid molecule termed a microRNA mimic.With hundreds of microRNAs identified and knowledge of their role in disease becoming clearer there is the prospect, over the coming years, to harness engineered microRNA therapeutics to revolutionise the way diseases are treated.Both types of engineered microRNA therapeutics have advanced into clinical development with human proof of concept achieved with an anti-miR targeting miR-122 (one of the most abundant microRNAs in human hepatocytes that is utilised by the hepatitis C virus to enable its function and replication). Rather than targeting individual proteins or enzymes involved in human disease, an opportunity now exists to modulate multiple different proteins/enzymes which act in concert in the progression of disease.
针对过表达的微小RNA或替代表达缺失的微小RNA，是治疗由微小RNA失调驱动的疾病的两种不同且新颖的方法。这可以通过对称为抗微小RNA的单链寡核苷酸或称为微小RNA模拟物的双链核酸分子进行化学修饰来实现。随着数百种微小RNA被鉴定出来，并且它们在疾病中的作用越来越清晰，在未来几年里，利用工程化微小RNA疗法彻底改变疾病治疗方式的前景很大。这两种工程化微小RNA疗法都已进入临床开发阶段，针对miR-122（人类肝细胞中最丰富的微小RNA之一，丙型肝炎病毒利用它来实现其功能和复制）的抗微小RNA已取得人体概念验证。现在有机会调节在疾病进展过程中协同作用的多种不同蛋白质/酶，而不是针对参与人类疾病的单个蛋白质或酶。
