LNA and alpha-L-LNA: towards therapeutic applications.
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.
Wengel
Jesper
J
Department of Chemistry, Nucleic Acid Center, University of Southern Denmark, Odense M, Denmark. jwe@chem.sdu.dk
Vester
Birte
B
Lundberg
Lars Bo
LB
Douthwaite
Stephen
S
Sørensen
Mads D
MD
Babu
B Ravindra
BR
Gait
Michael J
MJ
Arzumanov
Andrey
A
Petersen
Michael
M
Nielsen
Jakob T
JT
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
D021881:DNA, Catalytic; D015696:Gene Products, tat; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; C477371:locked nucleic acid; D054322:tat Gene Products, Human Immunodeficiency Virus