title: Vector design for liver-specific expression of multiple interfering RNAs that target hepatitis B virus transcripts.
abstract: RNA interference (RNAi) is a process that can target intracellular RNAs for degradation in a highly sequence-specific manner, making it a powerful tool that is being pursued in both research and therapeutic applications. Hepatitis B virus (HBV) is a serious public health problem in need of better treatment options, and aspects of its life cycle make it an excellent target for RNAi-based therapeutics. We have designed a vector that expresses interfering RNAs that target HBV transcripts, including both viral RNA replicative intermediates and mRNAs encoding viral proteins. Our vector design incorporates many features of endogenous microRNA (miRNA) gene organization that are proving useful for the development of reagents for RNAi. In particular, our vector contains an RNA pol II driven gene cassette that leads to tissue-specific expression and efficient processing of multiple interfering RNAs from a single transcript, without the co-expression of any protein product. This vector shows potent silencing of HBV targets in cell culture models of HBV infection. The vector design will be applicable to silencing of additional cellular or disease-related genes.
authors.affiliation: Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
authors.forename: Lindsey L
authors.initials: LL
authors.lastname: Snyder
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Esser
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Pachuk
authors.forename: Laura F
authors.initials: LF
authors.lastname: Steel
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012367:RNA, Viral; D014764:Viral Proteins; D012319:RNA Polymerase II