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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (1-2): 146-153    DOI: 10.13523/j.cb.1905007
综述     
肽核酸在病毒检测与治疗中的应用 *
孙恒1,王婧1,曾令高2,王建华1,**()
1 重庆大学生物工程学院 重庆 400044
2 重庆市食品药品检验检测研究院 重庆 401121
Application of Peptide Nucleic Acid in Virus Detection and Therapy
SUN Heng1,WANG Jing1,ZENG Ling-gao2,WANG Jian-hua1,**()
1 Bioengineering College of Chongqing University, Chongqing 400044, China
2 Chongqing Institute for Food and Drug Control, Chongqing 401121, China
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摘要：

肽核酸(peptide nucleic acid, PNA)是以多肽骨架取代糖磷酸主链的寡核苷酸类似物,又称第三代反义核酸。PNA的电中性多肽骨架结构,使其保留类似糖磷酸链寡核苷酸高靶标亲和力的同时,比糖磷酸主链具有更强的酶稳定性和热稳定性,已成为当今寡核苷酸类似物研究的热点。一方面,PNA对病毒的复制与突变水平具有的快速、有效和准确的检测性能,对疾病的进一步治疗具有重要意义;另一方面,基于PNA的序列特异性和剂量依赖性,能在基因水平上对病毒的生命周期进行特异性的调控,从而能更有效地实现抑制病毒在宿主细胞中生存和复制的目的。结合近十年来的文献,综述了PNA应用于不同病毒的检测及病毒性疾病治疗的最新进展和作用机制,以期为PNA的临床产品研发提供新的思路。
关键词： 肽核酸;  检测;  抗病毒    
Abstract:

Peptide nucleic acid (PNA) is an oligonucleotide analog that replaces the sugar phosphate backbone with polypeptide backbone, and known as a third-generation antisense nucleic acid. The electrically neutral polypeptide backbone structure of PNA enables it to retain the high target affinity of the sugar phosphate chain oligonucleotide, and at the same time, it has stronger enzyme stability and thermal stability than the sugar phosphate backbone, which has become the hotspot in the research of oligonucleotide analogues. On the one hand, the rapid, effective and accurate detection performance of PNA on virus replication and mutation level makes it of great significance for further treatment of diseases. On the other hand, the life cycle of the virus is regulated by the PNA based on its sequence specificity and dose dependency at the gene level. Therefore, as to effective inhibit the survival and replication of the virus in the host cell. The latest progress and mechanism of PNA in the detection of different viruses and the treatment of viral diseases has been reviewed based on the literature of the past decade, which is expected to provide new guidances and ideas for the development of clinical products of peptide nucleic acids.
Key words: Peptide nucleic acid    Detection    Antiviral
收稿日期: 2019-05-07 出版日期: 2020-03-27
ZTFLH:  Q819  
基金资助: * 国家自然科学基金委员会国家重大科研仪器研制项目(21827812);科技部“十三五”重大新药创制专项子课题资助项目(2017ZX09101001);重庆市社会事业与民生保障科技创新专项(cstc2017shms-xdny0033);重庆市技术创新与应用示范专项社会民生类重点研发项目(cstc2018jscx-mszdX0101)
通讯作者: 王建华     E-mail: wjh@cqu.edu.cn
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引用本文:

孙恒,王婧,曾令高,王建华. 肽核酸在病毒检测与治疗中的应用 *[J]. 中国生物工程杂志, 2020, 40(1-2): 146-153.

SUN Heng,WANG Jing,ZENG Ling-gao,WANG Jian-hua. Application of Peptide Nucleic Acid in Virus Detection and Therapy. China Biotechnology, 2020, 40(1-2): 146-153.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.1905007    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I1-2/146

图1  PNA和DNA的结构
PNA名称 序列(N→C端) 靶标 检测限 应用 参考文献
PANArray ACATCATCCATATAAC 逆转录酶M204V 102cps/ml HBV [12]
PNA-YIDD1 GTTATATCGATGATGTGG 逆转录酶204 0.01% HBV [11]
PNA-QCM TCCTTTTTT-OOO-TTTTTTCCT 基因组DNA序列 8.6pg/L HBV [14]
PNA-3a CACACATATCACCC 3a核心/E1区 1.8×10-12mol HCV [15]
PNA-SAM ATGTACCCCATGAGGTCGGC 核心/E1区 9.5pg/μl HCV [16]
PNA-HCV CCCAATTATACTTGCGGC M2基因 5% H1N1 [17]
bisPNA-AZO TCTCTTCC-AZO-CCTTCTCTTCCAGGA NS基因 6.0×104~6.0×105pfu/ml H1N1 [18]
PNA-ISH CTGGCTTTAATTTTA NL43WC001基因pol区 — HIV [19]
表1  用于病毒检测中PNA的碱基序列
PNA名称 序列(5'-3') 靶标 IC50 应用 参考文献
PNA 2052 TAGACGTAAAGATAC 衣壳化信号ε 10nmol DHBV [22]
PNA 2053 GCAATGTAGACGTAA 衣壳化信号ε 10nmol DHBV [22,25]
PNA-DR GCAGAGGTGAA pgRNA DR序列 — HBV [27]
肽-asPNA-寡核苷酸支架 AGGTGAAAAAGTTGCAT HBV DNA 1 814~1 830 — HBV [28]
PNA 6 TACGAGACCTCCCGGGG IRES 314~330 — HCV [30]
PNA 10 GTGCTCATGG IRES的IV环区域 54nmol HCV [31]
PNA-SL3 AGATGGAGCCACC X-RNA SL结构1~13 — HCV [32]
PNA-SL3-15 TAAGATGGAGCCACC X-RNA SL结构1~15 — HCV [32,41]
dbPNA TLTTTQTLLL dsRNA — 多种IAV亚型 [34]
TiO2·PL·DNA/PNA GCAAAAGCAGGGTAGA NP基因 3μg/ml H3N2 [35]
PNA-TAR TCCCAGGCTCAGATCT TAR 0.8μmol HIV [37-39]
PNA J3U5 TCGCGGCTTCATACA 3'-UTR 10 931~10 945 — JEV [40]
PNA J3U6 TCTCGCGGCTTCATACA 3'-UTR 10 931~10 947 — JEV [40]
PNA J3U2 TCGGCGCTCTGTGCC 3'-UTR 10 928~10 942 — JEV [40-41]
FS PNA AGCCCTGTAGACGAC PRF 13 458~13 472 4.4μmol SARS-CoV [41]
表2  用于病毒治疗中的PNA碱基序列
图2  PNA类似物结构[29]
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