title: Modification of small interfering RNAs to prevent off-target effects by the sense strand.
abstract: OBJECTIVE
  There is a broad therapeutic potential for the application of small interfering RNAs (siRNAs). However, one has to ensure that siRNAs act specifically, only targeting the expression of one gene. Off-target effects raised by the sense strand have to be eliminated.
  
  
  RESULTS
  We examined a particular bidirectional siRNA molecule, able to knockdown intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor-1 (TNFR-1) by the sense or antisense strand, respectively. Transfection of human venous endothelial cells with an unmodified siRNA molecule led to equal silencing of ICAM-1 and TNFR-1. In contrast, modified siRNA was able to knockdown ICAM-1 and TNFR-1 separately, with only the antisense strand.
  
  
  CONCLUSIONS
  We found the modified siRNAs to inhibit off-target effects originated by the sense strand. Our approach demonstrates one possibility to modify siRNAs before starting a clinical approach to eliminate off-target effects.
authors.affiliation: Department of Thoracic, Cardiac, and Vascular Surgery, University of Tuebingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nolte
authors.forename: Kathrin
authors.initials: K
authors.lastname: Ott
authors.forename: Jacques
authors.initials: J
authors.lastname: Rohayem
authors.forename: Tobias
authors.initials: T
authors.lastname: Walker
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wendel
mesh_terms: D003062:Codon / Q000235:genetics*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D003062:Codon; D019040:E-Selectin; D034741:RNA, Small Interfering; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1