RNA药物的发展及其在水产上的应用

doi:10.13560/j.cnki.biotech.bull.1985.2020-0340

摘要/Abstract

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。

关键词: 水产动物疾病, CRISPR, RNA干扰, RNA药物

Abstract:

RNA-based RNA interference and genome editing technologies are used in many fields. Because of its specificity,RNA becomes a candidate molecule for the development of target drugs. The research and development of RNA-based disease treatment drugs have been developing rapidly in recent years. With the development of the aquaculture industry,the losses caused by the diseases have become more and more serious. Studies on using small-molecule RNA drugs to effectively protect aquatic animals against viruses and parasites have also achieved some results. In this review,we summarized the mechanism and principle of RNA interference and CRISPR as well as the latest developments and applications in inhibiting aquatic animal viruses combined with our research results,and the current related RNA drugs are summarized,aiming for providing references for future research on the development of RNA drugs in aquatic animals.

Key words: aquatic animal disease, CRISPR, RNA interference, RNA drugs

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.

图/表 4

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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^[51]
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^[5]
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^[52]
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

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^[51]
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^[5]
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^[52]
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^[54]	巨细胞病毒视网膜炎（CMV）免疫功能不全	ASOs	Ionis Pharmaceuticals	1998/8/26
Macugen	Pegaptanib^[55]	年龄相关性黄斑变性（AMD）	Aptamer	Pfizer	2004/9/17
Kynamro	Mipomersen^[56]	治疗纯合子型家族性高胆固醇血症（HoFH）	ASOs	Sanofi-aventis	2013/1/29
Defitelio	Defibrotide^[57]	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^[58]	治疗外显子51跳跃型杜氏肌营养不良（DMD）	ASOs	Pfizer	2016/9/19
Spinraza	Nusinersen^[59]	治疗脊髓性肌萎缩症（SMA）	ASOs	Biogen Idec and Ionis Pharmaceuticals	2016/12/23
Onpattro	Patisiran^[60]	治疗转甲状腺素蛋白淀粉样变性（hATTR）	siRNA	Alnylam	2018/8/10

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^[54]	巨细胞病毒视网膜炎（CMV）免疫功能不全	ASOs	Ionis Pharmaceuticals	1998/8/26
Macugen	Pegaptanib^[55]	年龄相关性黄斑变性（AMD）	Aptamer	Pfizer	2004/9/17
Kynamro	Mipomersen^[56]	治疗纯合子型家族性高胆固醇血症（HoFH）	ASOs	Sanofi-aventis	2013/1/29
Defitelio	Defibrotide^[57]	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^[58]	治疗外显子51跳跃型杜氏肌营养不良（DMD）	ASOs	Pfizer	2016/9/19
Spinraza	Nusinersen^[59]	治疗脊髓性肌萎缩症（SMA）	ASOs	Biogen Idec and Ionis Pharmaceuticals	2016/12/23
Onpattro	Patisiran^[60]	治疗转甲状腺素蛋白淀粉样变性（hATTR）	siRNA	Alnylam	2018/8/10