title: Adenosine modification may be preferred for reducing siRNA immune stimulation.
abstract: The immune stimulation induced by short interfering RNAs (siRNAs) has been reported to be quieted or abrogated by methoxy or fluoro modifications of the 2' position of the ribose sugar. However, variables such as the type of modification, nucleotide preference, and strand bias have not been systematically evaluated. Here, we report the results of a screen of several modified siRNAs via a human peripheral blood monocyte cytokine induction assay. Unlike corresponding modifications of guanosine, cytidine, or uridine, 2'-fluoro modification of adenosine significantly reduced cytokine induction while retaining siRNA knockdown activity. The results of this study suggest adenosine as an optimal target for modification.
authors.affiliation: Sirna Therapeutics, a wholly owned subsidiary of Merck and Co., San Francisco, California, USA.
authors.forename: Raymond V
authors.initials: RV
authors.lastname: Fucini
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Haringsma
authors.forename: Patricia
authors.initials: P
authors.lastname: Deng
authors.forename: W Michael
authors.initials: WM
authors.lastname: Flanagan
authors.forename: Aarron T
authors.initials: AT
authors.lastname: Willingham
mesh_terms: D000241:Adenosine / Q000737:chemistry*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D034741:RNA, Small Interfering / Q000737:chemistry / Q000276:immunology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D001616:beta-Galactosidase; D000241:Adenosine