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摘要: 单纯疱疹病毒1型（herpes simplex virus type 1，HSV-1）是一种能够在各类人群中携带和传播并能引起包括口唇疱疹、荚膜炎、角膜炎和病毒性脑炎等疾病的重要病原体。虽然已有多种类型的HSV-1疫苗处于研发的不同阶段，但仍没有商业化的疫苗上市销售。临床上使用的特异性抗HSV-1药物如阿昔洛韦、伐昔洛韦和喷昔洛韦等也面临严重的抗药性威胁，开发新的特异性抗HSV-1药物是当前所面临的主要任务之一。siRNA是一种长度为20～25 核苷酸的双链RNA，通过在转录后水平上沉默基因表达发挥干扰作用。siRNA作为一种新的、有潜力的抗病毒药物备受关注，发展也较为迅速。综述近年来siRNA在抗HSV-1方面的研究进展，包括靶向HSV-1关键基因和HSV-1互作的宿主细胞基因的siRNA设计、递送和靶向策略。Abstract: HSV-1 is an important pathogen that can be carried and transmitted in various populations and can cause diseases including herpes labialis, capsulatus, keratitis and viral encephalitis. Although there are several types of HSV-1 vaccines in various stages of development, there is still no commercially available vaccine on the market. The specific anti-HSV-1 drugs used in clinical practice, such as acyclovir, valaciclovir and peniclovir, are also facing the serious threat of resistance. The development of new specific anti-HSV-1 drugs is one of the main tasks currently faced. siRNA is a double-stranded RNA with a length of 20-25 nucleotides that plays an interfering role by silencing gene expression at the post-transcriptional level. As a new and potential antiviral drug, siRNA has attracted much attention and developed rapidly. In this paper, we review the recent progress of siRNA in anti-HSV-1 research, including the design, delivery and targeting strategies of siRNA targeting key HSV-1 genes and HSV-1 interacting host cell genes.
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Key words:
- siRNA /
- HSV-1 /
- Research Progress
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表 1 靶向HSV-1编码基因的siRNA
Table 1. Summary of siRNAs targeting HSV-1-encoded genes
靶基因 siRNA 正向 （5′-3′） 反向 （5′-3′） 干扰效率（%） 参考文献 UL18 siUL18-1 GCACCGUUAACCUUCGCAATT UUGCGAAGGUUAACGGUGCTT 86.78 [25] siUL18-2 GUCCUUAACAUGGUUUACUTT AGUAAACCAUGUUAAGGACTT 60.00 siUL18-3 CCAUCAUCCUUACGCUAAUTT AUUAGCGUAAGGAUGAUGGTT 87.25 siUL18-4 CCCGUUAUACGCUAUCCCUAA AGGGAUAGCGUAUAACGGGGG 65.00 UL19 siUL19-1 CCAGCGACGUACAGUUUAATT UUAAACUGUACGUCGCUGGCG 79.71 siUL19-2 CUUUUGUGCCGAUGCATT UGCAUCGGCAACAACAAAGTT 81.52 siUL19-3 CGACCGACGUCAACUACUUTT AAGUAGUUGACGUCGGUCGTT 81.52 siUL19-4 CCAGCGACGUACAGUUUAATT UUAAACUGUACGUCGCUGGTT 78.86 UL26 siUL26-1 CCGUUAACAACAUGAUGCUTT AGCAUCAUGUUGGUUAACGGCG 40.00 siUL26-2 CCGAUUUGUUCGUCUCUCATT UGAGAGACGAACAAAUCGGCG 81.21 siUL26-3 CUGUUGUACCUGAUCACCAAC UGGUGAUCAGGUACAACAGGC NC siUL26-4 CCGUUAACAACAUGAUGCUGC AGCAUCAUGUUGGUUAACGGCG 10.00 UL26.5 siUL26.5 CCGAUUUGUUCGUCUCUCAUU UUGGCUAAACAAGCAGAGAGU 52.12 UL28 shRNAUL28 GATCCGCAGGTGCAGACCTATG
TGTTTTCAAGAGAACACATAGG
TCTGCACCTGCTTTTTTGGAAANC DAY1 50.00 [29] DAY2 70.00 DAY3 60.00 DAY4 40.00 UL29 shRNAUL29 GATCCGCAATCAATTCCAACCG
GTGCTTCAAGAGAGCACCGGTT
GGAATTGATTGCTTTTTTGGAAANC DAY1 60.00 DAY2 80.00 DAY3 60.00 DAY4 50.00 UL30 siRNA-4 GGUACAACAUCAUCAACUUTT AAGUUGAUGAUGUUGUACCTT 6 h 60.00 [40] 12 h 80.00 UL35 siUL35-1 CACGCAAACAACACGUUUATT UAACGUGUUGUUGCGUGGG 50.00 [25] siUL35-2 GCCACCAAUAACUCUCAGUTT ACUGAGAGUUAUUGGUGGCCA 55.95 siUL35-3 CUCUCAGUUUAUCAUGGAUTT AUCCAUGAUAAACUGAGAGTT 22.00 siUL35-4 GUUUGUCGUCGAGAACCUTT AGGUUCUCGAACGACAAACGG 30.00 UL38 siUL38-1 GGCCUAGUGUCGUUUAACUTT AGUUAAACGACACUAGGCCCG NC [25] siUL38-2 GGAUCACCAAACCGAUUCATT UGAAUCGUGUUGGUGAUCCCGG 10.00 siUL38-3 GCGUUUCUGUACCUGGUAUTT AUACCAGGUACAGAAACGCCG 82.48 siUL38-4 GUUGUGUGUACGUGAUCAATT UUGAUCACGUACACACAACAC NC UL39
siRNA1 CUGCACCAUGAUCAUCGACdTdT GUCGAUGAUCAUGGUGCAGdTdT 29.63 [33] siRNA2 AUCGGCCCUGAAGUAUGAGdTdT CUCAUACUUCAGGGCCGAUUG 27.07 siRNA3 GCGCUGCGACAAUAUCUUCdTdT GAAGAUAUUGUCGCAGCGCUG NC siRNA4 CCAUAGCCAAUCCAUGACCdTdT GGUCAUGGAUUGGCUAUGGUC NC UL40 siRNA-1 GACGACCUGGUUACGGAAAdTdT UUUCCGUAACCAGGUCGUCGG 2.73 [30] siRNA-2 AAUGCAUCGAAGUCGUACAdTdT UGUACGACUUCGAUGCAUUCC 69.83 siRNA-3 UCACCUGCCAGUCAAACGAdTdT UCGUUUGACUGGCAGGUGACC 67.94 siRNA-4 AAAUUGGUGUGUUUGUCGGUG AAAUUGGUGUGUUUGUCGGUG 81.31 ICP4 siRNA GCAACAGCAGCUCCUUCAUdTdT dTdTCGUUGUCGUCGAGGAAGUA 12 h 69.00 24 h 95.00 VP16 siRNA-1 GGUACUUUAUGGUGUUGAUTT AUCAACACCAUAAAGUACCTT NC [31，40] 
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表 2 靶向宿主基因与HSV-1相互作用的siRNA
Table 2. Summary of siRNA targeting host genes interacting with HSV-1
靶基因 siRNA 正向（5′-3′） 参考文献 INSM1 siINSM1 UCCGCAAGCUGCACUUCGATT [45] SNF2H siRNA5 GGAAUGGUAUACUCGGAUA [48] siRNA6 GGGCAAA UAGAUUCGAGUA siRNA7 GGAUUUACCAAUUGGAAUA siRNA8 GUUCUUUCCUCCACGUUUA REST siREST GUGAUACUGUAGAUUACAC [49] coREST sicoREST AAGAUUGUCCCGUUCUUGACU [59] TSG101 siTSG101 CCUCCAGUCUUCUCUCGUCTT [52] ALIX siALIX GCCGCUGGUGAAGUUCAUCTT
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