Optimizing synthetic miRNA minigene architecture for efficient miRNA hairpin concatenation and multi-target gene knockdown
作者: Francis RoussetPatrick SalmonSimon BredlOphélie CherpinMarta CoelhoRenier MyburghMarco AlessandriniMichael PernyMarta RoccioRoberto F. SpeckPascal SennKarl Heinz Krause
作者单位: 1Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva Switzerland
2Department of Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland
3Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland
4Division of Hematology, University Hospital of Zurich, Zurich, Switzerland
5Department of Otorhinolaryngology, Inselspital and University of Bern, Bern, Switzerland
6Department of Head and Neck Surgery, University Hospital of Geneva, Geneva, Switzerland
刊名: Molecular Therapy - Nucleic Acids, 2018
来源数据库: Elsevier Journal
DOI: 10.1016/j.omtn.2018.12.004
原始语种摘要: Abstract(#br)Synthetic miRNA minigenes, SMIG, have a major potential for molecular therapy, however their optimal architecture still needs to be determined. We have previously optimized the stem structure of miRNA hairpins for efficient gene knockdown. Here we investigate the overall architecture of SMIG driven by polymerase II-dependent promoters. When miRNA hairpins were placed directly behind the promoter, gene knockdown was inefficient as compared to constructs containing an intercalated sequence (“spacer”). Spacer sequence was relevant for knockdown efficiency and concatenation potential: GFP–based sequences (even when truncated or including stop codons) were particularly efficient. In contrast, a spacer of similar length based on a CD4 intronic sequence was entirely inefficient....
全文获取路径: Elsevier  (合作)
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关键词翻译
关键词翻译
  • knockdown 击倒
  • efficient 有用的
  • architecture 构造
  • target 目标
  • demonstrated 探明的储量
  • spacer 垫片
  • concatenation 级联
  • investigate 
  • sequence 次序
  • potential