Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.
A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.
Sullivan
S M
SM
Vestar, Inc., San Dimas, California.
Gieseler
R K
RK
Lenzner
S
S
Ruppert
J
J
Gabrysiak
T G
TG
Peters
J H
JH
Cox
G
G
Richer
L
L
Martin
W J
WJ
Scolaro
M J
MJ
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D016373:DNA, Antisense / Q000494:pharmacology*; D004274:DNA, Recombinant / Q000494:pharmacology*; D004337:Drug Carriers; D004705:Endocytosis / Q000187:drug effects; D015756:Genes, tat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000382:microbiology; D008081:Liposomes / Q000493:pharmacokinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012326:RNA Splicing; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D000998:Antiviral Agents; D016373:DNA, Antisense; D004274:DNA, Recombinant; D004337:Drug Carriers; D008081:Liposomes; D016376:Oligonucleotides, Antisense