Self-stabilized antisense oligodeoxynucleotide phosphorothioates: properties and anti-HIV activity.
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.
Hybridon, Inc., Worcester, MA 01605.
J Y
JY
Tang
J
J
Temsamani
S
S
Agrawal
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001769:Blood; D002417:Cattle; D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000378:metabolism; D004355:Drug Stability; D015750:Genes, gag; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D016914:Ribonuclease H / Q000378:metabolism; D013873:Thionucleotides; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D012367:RNA, Viral; D013873:Thionucleotides; D004256:DNA Polymerase I; D016914:Ribonuclease H; D010727:Phosphoric Diester Hydrolases