Self-stabilized Antisense Oligodeoxynucleotide Phosphorothioates: Properties and anti-HIV Activity

Nucleic Acids Res. 1993 Jun 11;21(11):2729-35. doi: 10.1093/nar/21.11.2729.

Abstract

A new class of oligodeoxyribonucleotides has been designed, referred to here as 'self-stabilized' oligonucleotides. These oligonucleotides have hairpin loop structures at their 3' ends, and show increased resistance to degradation by snake venom phosphodiesterase, DNA polymerase I and fetal bovine serum. The self-stabilized region of the oligonucleotide does not interfere in hybridization with complementary nucleic acids as shown by melting temperature, mobility-shift and RNase H cleavage studies. Various self-stabilized oligonucleotides containing increasingly stable hairpin loop regions were studied for their anti-HIV activity. Pharmacokinetic and stability studies in mice showed increased in vivo persistence of self-stabilized oligonucleotides with respect to their linear counterparts.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Blood
  • Cattle
  • Cells, Cultured
  • DNA Polymerase I / metabolism
  • Drug Stability
  • Genes, gag
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Lymphocytes
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • Nucleic Acid Hybridization
  • Oligonucleotides, Antisense / chemical synthesis
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / pharmacology*
  • Oligoribonucleotides / metabolism
  • Phosphoric Diester Hydrolases / metabolism
  • RNA, Viral / metabolism
  • Ribonuclease H / metabolism
  • Thionucleotides*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Oligonucleotides, Antisense
  • Oligoribonucleotides
  • RNA, Viral
  • Thionucleotides
  • DNA Polymerase I
  • Ribonuclease H
  • Phosphoric Diester Hydrolases