title: Application of small interfering RNAs modified by unlocked nucleic acid (UNA) to inhibit the heart-pathogenic coxsackievirus B3.
abstract: This study describes the first application of unlocked nucleic acid (UNA)-modified small interfering RNAs (siRNAs) directed against a medically relevant target, the coxsackievirus B3. We systematically analyzed the impact of different siRNA modification patterns and observed good compatibility of the introduction of UNA with the maintenance of high antiviral activity. Additionally, the polarity of an siRNA was successfully reversed by modulating the relative stability of the termini with locked nucleic acid (LNA) and UNA as shown in a reporter assay. The potency of the reversed siRNA against the full-length target was, however, too low to inhibit the infectious virus. Altogether, combined modification of siRNAs with LNA und UNA provides a promising approach to alter and improve properties of an siRNA.
authors.affiliation: Institute for Virology, Campus Benjamin Franklin, Charité-University Medicine, Berlin, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Werk
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.forename: Suzy L
authors.initials: SL
authors.lastname: Wengel
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Grunert
authors.forename: Heinz
authors.initials: H
authors.lastname: Zeichhardt
authors.forename: Jens
authors.initials: J
authors.lastname: Kurreck
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D029822:Enterovirus B, Human / Q000187:drug effects* / Q000235:genetics; D006321:Heart / Q000821:virology*; D009696:Nucleic Acids / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D009696:Nucleic Acids; D034741:RNA, Small Interfering