title: LNA and alpha-L-LNA: towards therapeutic applications.
abstract: LNA and alpha-L-LNA are promising candidates for the development of efficient oligonucleotide-based therapeutic agents. Here, we report dose-dependent inhibition of HIV-1 Tat-dependent trans activation by a 12-mer chimeric alpha-L-LNA/DNA oligomer. This oligomer exhibits a dose-dependency similar to that of the corresponding 12-mer chimeric LNA/2'-O-Me-RNA oligomer. In addition, we show that incorporation of alpha-L-LNA or LNA monomers into each of the two binding arms of a "10-23" DNAzyme markedly increases cleavage of the target RNA.
authors.affiliation: Department of Chemistry, Nucleic Acid Center, University of Southern Denmark, Odense M, Denmark. jwe@chem.sdu.dk
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
authors.forename: Birte
authors.initials: B
authors.lastname: Vester
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Lundberg
authors.forename: Stephen
authors.initials: S
authors.lastname: Douthwaite
authors.forename: Mads D
authors.initials: MD
authors.lastname: Sørensen
authors.forename: B Ravindra
authors.initials: BR
authors.lastname: Babu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gait
authors.forename: Andrey
authors.initials: A
authors.lastname: Arzumanov
authors.forename: Michael
authors.initials: M
authors.lastname: Petersen
authors.forename: Jakob T
authors.initials: JT
authors.lastname: Nielsen
mesh_terms: D001483:Base Sequence; D002678:Chimera; D021881:DNA, Catalytic / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000627:therapeutic use*; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D021881:DNA, Catalytic; D015696:Gene Products, tat; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D054322:tat Gene Products, Human Immunodeficiency Virus