LNA and alpha-L-LNA: towards therapeutic applications

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):601-4. doi: 10.1081/NCN-120021963.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chimera
  • DNA, Catalytic / metabolism
  • Gene Products, tat / metabolism
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • Nucleic Acid Conformation
  • Oligonucleotides
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / therapeutic use*
  • Transcriptional Activation
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • DNA, Catalytic
  • Gene Products, tat
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • locked nucleic acid
  • tat Gene Products, Human Immunodeficiency Virus