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学科主题: 药学
题名:
Caged circular antisense oligonucleotides for photomodulation of RNA digestion and gene expression in cells
作者: Wu, Li; Wang, Yuan; Wu, Junzhou; Lv, Cong; Wang, Jie; Tang, Xinjing
刊名: NUCLEIC ACIDS RESEARCH
发表日期: 2013
DOI: 10.1093/nar/gks996
卷: 41, 期:1, 页:677-686
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: LIGHT-ACTIVATED OLIGONUCLEOTIDES ; ZEBRAFISH EMBRYOS ; MAMMALIAN-CELLS ; DNA ; PHOTOREGULATION ; HYBRIDIZATION ; TRANSCRIPTION ; INTERFERENCE ; AZOBENZENE ; CLEAVAGE
英文摘要:

We synthesized three 20mer caged circular antisense oligodeoxynucleotides (R20, R20B2 and R20B4) with a photocleavable linker and an amide bond linker between two 10mer oligodeoxynucleotides. With these caged circular antisense oligodeoxynucleotides, RNA-binding affinity and its digestion by ribonuclease H were readily photomodulated. RNA cleavage rates were upregulated similar to 43-, 25- and 15-fold for R20, R20B2 and R20B4, respectively, upon light activation in vitro. R20B2 and R20B4 with 2- or 4-nt gaps in the target RNA lost their ability to bind the target RNA even though a small amount of RNA digestion was still observed. The loss of binding ability indicated promising gene photoregulation through a non-enzymatic strategy. To test this strategy, three caged circular antisense oligonucleotides (PS1, PS2 and PS3) with 2′-OMe RNA and phosphorothioate modifications were synthesized to target GFP expression. Upon light activation, photomodulation of target hybridization and GFP expression in cells was successfully achieved with PS1, PS2 and PS3. These caged circular antisense oligonucleotides show promising applications of photomodulating gene expression through both ribonuclease H and non-enzyme involved antisense strategies.

语种: 英语
所属项目编号: 21072015 ; 2012CB720600 ; NCET-10-0203 ; 2012M510290 ; 21072015 ; 2012M510290
项目资助者: National Science Foundation of China (NSFC) ; National Basic Research Program of China [&prime ; 973&prime ; Program] ; Program for New Century Excellent Talents in University ; China Postdoctoral Science Foundation (CPSF) ; NSFC ; CPSF
WOS记录号: WOS:000312889900088
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66010
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wu, Li,Wang, Yuan,Wu, Junzhou,et al. Caged circular antisense oligonucleotides for photomodulation of RNA digestion and gene expression in cells[J]. NUCLEIC ACIDS RESEARCH,2013,41(1):677-686.
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