RNA therapeutics: RNAi and antisense mechanisms and clinical applications.
RNA therapeutics: RNAi and antisense mechanisms and clinical applications.
复制标题
DOI：
10.14304/surya.jpr.v4n7.5
复制
发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Chery J
中科院分区：
文献类型：
--
作者：
Chery J
RNA疗法是指利用寡核苷酸主要靶向核糖核酸（RNA）进行治疗或在研究中阐明基因的功能。由于寡核苷酸的作用机制和化学性质，寡核苷酸不同于其他药理模式，如主要针对蛋白质的小分子和抗体。核酸有两种形式：脱氧核糖核酸（DNA）和核糖核酸（RNA）。虽然DNA更稳定，但RNA提供了更多的结构多样性，从编码蛋白质的信使RNA （mRNA）到非编码RNA、微RNA （miRNA）、转移RNA （tRNA）、短干扰RNA （sirna）、核糖体RNA （rRNA）和长链非编码RNA （lncRNAs）。随着我们对各种RNA的了解的加深，研究人员一直在寻求靶向RNA，因为据估计80%的基因组是转录的。这些转录本包括非编码rna，如mirna和sirna，它们在基因调控中发挥关键作用，在遗传信息从DNA转移到蛋白质的过程中发挥关键作用，这是生物学中心法则的最终产物。目前主要有两种靶向RNA的方法：双链RNA介导干扰（RNAi）和反义寡核苷酸（ASO）。这两种方法目前都处于临床试验阶段，用于靶向与各种疾病有关的rna，如癌症和神经变性。事实上，针对脊髓性肌萎缩症和肌萎缩侧索硬化症的ASOs在临床试验中已经显示出积极的效果。ASOs的优点包括更高的亲和力，这是由于化学修饰的发展增加了亲和力，选择性，同时降低了脱靶效应引起的毒性。本文综述了RNA医学目前应用的主要治疗方法，重点介绍了RNAi和ASOs。
RNA therapeutics refers to the use of oligonucleotides to target primarily ribonucleic acids (RNA) for therapeutic efforts or in research studies to elucidate functions of genes. Oligonucleotides are distinct from other pharmacological modalities, such as small molecules and antibodies that target mainly proteins, due to their mechanisms of action and chemical properties. Nucleic acids come in two forms: deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). Although DNA is more stable, RNA offers more structural variety ranging from messenger RNA (mRNA) that codes for protein to non-coding RNAs, microRNA (miRNA), transfer RNA (tRNA), short interfering RNAs (siRNAs), ribosomal RNA (rRNA), and long-noncoding RNAs (lncRNAs). As our understanding of the wide variety of RNAs deepens, researchers have sought to target RNA since >80% of the genome is estimated to be transcribed. These transcripts include non-coding RNAs such as miRNAs and siRNAs that function in gene regulation by playing key roles in the transfer of genetic information from DNA to protein, the final product of the central dogma in biology. Currently there are two main approaches used to target RNA: double stranded RNA-mediated interference (RNAi) and antisense oligonucleotides (ASO). Both approaches are currently in clinical trials for targeting of RNAs involved in various diseases, such as cancer and neurodegeneration. In fact, ASOs targeting spinal muscular atrophy and amyotrophic lateral sclerosis have shown positive results in clinical trials. Advantages of ASOs include higher affinity due to the development of chemical modifications that increase affinity, selectivity while decreasing toxicity due to off-target effects. This review will highlight the major therapeutic approaches of RNA medicine currently being applied with a focus on RNAi and ASOs.