Pereira Tiago Campos, Lopes-Cendes Iscia
Department of Biology, Sciences and Languages of Ribeirao Preto - FFCLRP, University of Sao Paulo - USP, Ribeirao Preto, SP, Brazil.
Cent Nerv Syst Agents Med Chem. 2012 Sep;12(3):217-32. doi: 10.2174/187152412802430138.
An emerging new category of therapeutic agents based on ribonucleic acid has emerged and shown very promising in vitro, animal and pre-clinical results, known as small interfering RNAs (siRNAs), microRNAs mimics (miRNA mimics) and their derivates. siRNAs are small RNA molecules that promote potent and specific silencing of mutant, exogenous or aberrant genes through a mechanism known as RNA interference. These agents have called special attention to medicine since they have been used to experimentally treat a series of neurological conditions with distinct etiologies such as prion, viral, bacterial, fungal, genetic disorders and others. siRNAs have also been tested in other scenarios such as: control of anxiety, alcohol consumption, drug-receptor blockage and inhibition of pain signaling. Although in a much earlier stage, miRNAs mimics, anti-miRs and small activating RNAs (saRNAs) also promise novel therapeutic approaches to control gene expression. In this review we intend to introduce clinicians and medical researchers to the most recent advances in the world of siRNA- and miRNA-mediated gene control, its history, applications in cells, animals and humans, delivery methods (an yet unsolved hurdle), current status and possible applications in future clinical practice.
一类基于核糖核酸的新型治疗药物已经出现,并在体外、动物实验和临床前研究中显示出非常有前景的结果,这类药物包括小干扰RNA(siRNA)、微小RNA模拟物(miRNA模拟物)及其衍生物。siRNA是小RNA分子,通过一种称为RNA干扰的机制促进对突变、外源或异常基因的有效和特异性沉默。自从这些药物被用于实验性治疗一系列病因各异的神经系统疾病(如朊病毒、病毒、细菌、真菌、遗传疾病等)以来,它们引起了医学界的特别关注。siRNA也在其他场景中进行了测试,如:控制焦虑、饮酒、药物受体阻断和抑制疼痛信号传导。尽管处于更早的阶段,但miRNA模拟物、抗miR和小激活RNA(saRNA)也有望成为控制基因表达的新型治疗方法。在这篇综述中,我们打算向临床医生和医学研究人员介绍siRNA和miRNA介导的基因控制领域的最新进展、其历史、在细胞、动物和人类中的应用、递送方法(一个尚未解决的障碍)、当前状况以及在未来临床实践中的可能应用。