生物技术通报 ›› 2021, Vol. 37 ›› Issue (2): 203-215.doi: 10.13560/j.cnki.biotech.bull.1985.2020-0340
潘银来1,2(), 邱春辉1,3, 王艺磊1,4, 张子平1,2,5()
收稿日期:
2020-03-25
出版日期:
2021-02-26
发布日期:
2021-02-26
作者简介:
潘银来,男,硕士研究生,研究方向:水产疫苗;E-mail: 基金资助:
PAN Yin-lai1,2(), QIU Chun-hui1,3, WANG Yi-lei1,4, ZHANG Zi-ping1,2,5()
Received:
2020-03-25
Published:
2021-02-26
Online:
2021-02-26
摘要:
基于RNA的RNA干扰和基因组编辑技术被应用于许多领域。由于其作用的特异性,使RNA成为靶点药物的候选分子。基于RNA的疾病治疗药物的研发近年来有了迅速的发展。随着养殖业的发展,病害引起的损失日益严重。运用小分子RNA药物有效保护水产动物抵抗病毒、寄生虫等的危害的研究也取得了一些成果。综述了RNA干扰和CRISPR的作用机制、原理及其在抑制水产动物病毒等方面的最新发展和应用,并结合我们的研究成果进行阐述,同时对目前相关的RNA药物进行总结,旨为今后更好地研究水产动物的RNA药物提供参考。
潘银来, 邱春辉, 王艺磊, 张子平. RNA药物的发展及其在水产上的应用[J]. 生物技术通报, 2021, 37(2): 203-215.
PAN Yin-lai, QIU Chun-hui, WANG Yi-lei, ZHANG Zi-ping. Development of RNA Drugs and Its Application in Aquaculture[J]. Biotechnology Bulletin, 2021, 37(2): 203-215.
RNA的药物类型 | 靶标 | 作用原理 |
---|---|---|
siRNA | mRNA | siRNA并入RISC(RNA诱导的沉默复合体)中,然后与靶基因CDS区(大部分)或UTR区配对,降解靶基因mRNA,完全抑制靶基因在细胞内的翻译表达[ |
ASOs | mRNA,pre-mRNA,miRNA | 靶向特异性的互补(编码或非编码RNA)和mRNA结合,激活RNAse H,水解mRNA[ |
Aptamers | 蛋白质或有机小分子 | 常被称为“化学抗体”,具有与抗体相似的高特异性和结合亲和性,可以和不同靶标如有机小分子或蛋白质等进行结合,阻止其发挥功能[ |
miRNA | mRNA | miRNA通过和靶基因mRNA碱基配对引导RISC降解mRNA或阻止其翻译。与siRNA的不同在于,miRNA与靶mRNA一般不是完全配对,并且多结合与3'UTR区 |
表1 RNA的药物的作用机理
RNA的药物类型 | 靶标 | 作用原理 |
---|---|---|
siRNA | mRNA | siRNA并入RISC(RNA诱导的沉默复合体)中,然后与靶基因CDS区(大部分)或UTR区配对,降解靶基因mRNA,完全抑制靶基因在细胞内的翻译表达[ |
ASOs | mRNA,pre-mRNA,miRNA | 靶向特异性的互补(编码或非编码RNA)和mRNA结合,激活RNAse H,水解mRNA[ |
Aptamers | 蛋白质或有机小分子 | 常被称为“化学抗体”,具有与抗体相似的高特异性和结合亲和性,可以和不同靶标如有机小分子或蛋白质等进行结合,阻止其发挥功能[ |
miRNA | mRNA | miRNA通过和靶基因mRNA碱基配对引导RISC降解mRNA或阻止其翻译。与siRNA的不同在于,miRNA与靶mRNA一般不是完全配对,并且多结合与3'UTR区 |
商品名 | 活性成分 | 治疗疾病 | 药物类型 | 生产公司 | FDA批准日期 |
---|---|---|---|---|---|
Vitravene Preservative Free | Fomivirsen[ | 巨细胞病毒视网膜炎(CMV)免疫功能不全 | ASOs | Ionis Pharmaceuticals | 1998/8/26 |
Macugen | Pegaptanib[ | 年龄相关性黄斑变性(AMD) | Aptamer | Pfizer | 2004/9/17 |
Kynamro | Mipomersen[ | 治疗纯合子型家族性高胆固醇血症(HoFH) | ASOs | Sanofi-aventis | 2013/1/29 |
Defitelio | Defibrotide[ | 治疗肝小静脉闭塞病(VOD),和造血干细胞移植(HSCT)后有肾或肺功能失调 | ASOs | Jazz Pharmaceuticals plc | 2016/3/30 |
Exondys 51 | Eteplirsen[ | 治疗外显子51跳跃型杜氏肌营养不良(DMD) | ASOs | Pfizer | 2016/9/19 |
Spinraza | Nusinersen[ | 治疗脊髓性肌萎缩症(SMA) | ASOs | Biogen Idec and Ionis Pharmaceuticals | 2016/12/23 |
Onpattro | Patisiran[ | 治疗转甲状腺素蛋白淀粉样变性(hATTR) | siRNA | Alnylam | 2018/8/10 |
表2 已被批准上市生产RNA相关药物
商品名 | 活性成分 | 治疗疾病 | 药物类型 | 生产公司 | FDA批准日期 |
---|---|---|---|---|---|
Vitravene Preservative Free | Fomivirsen[ | 巨细胞病毒视网膜炎(CMV)免疫功能不全 | ASOs | Ionis Pharmaceuticals | 1998/8/26 |
Macugen | Pegaptanib[ | 年龄相关性黄斑变性(AMD) | Aptamer | Pfizer | 2004/9/17 |
Kynamro | Mipomersen[ | 治疗纯合子型家族性高胆固醇血症(HoFH) | ASOs | Sanofi-aventis | 2013/1/29 |
Defitelio | Defibrotide[ | 治疗肝小静脉闭塞病(VOD),和造血干细胞移植(HSCT)后有肾或肺功能失调 | ASOs | Jazz Pharmaceuticals plc | 2016/3/30 |
Exondys 51 | Eteplirsen[ | 治疗外显子51跳跃型杜氏肌营养不良(DMD) | ASOs | Pfizer | 2016/9/19 |
Spinraza | Nusinersen[ | 治疗脊髓性肌萎缩症(SMA) | ASOs | Biogen Idec and Ionis Pharmaceuticals | 2016/12/23 |
Onpattro | Patisiran[ | 治疗转甲状腺素蛋白淀粉样变性(hATTR) | siRNA | Alnylam | 2018/8/10 |
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