Antibody-targeted liposomes containing oligodeoxyribonucleotides complementary to viral RNA selectively inhibit viral replication.
Mouse L929 cells were incubated with antibody-targeted liposomes containing oligodeoxyribonucleotides (oligomers). When the oligomer was a 15-mer complementary to the 5'-end region of the mRNA encoding the N protein of vesicular stomatitis virus, the cells became less permissive for multiplication of that virus; greater than 95% reduction of viral multiplication was achieved. Protection was not seen for "empty" liposomes, liposomes containing a random oligomer sequence, or liposomes containing a sequence complementary to the 5' end of c-myc protooncogene mRNA targeted by the same antibody, nor was it seen when the liposomes containing the N-protein antisense oligomer were targeted by an antibody that does not bind to L929 cells. Antibody-bearing liposomes containing antisense oligomers thus have a double specificity: a particular cell selected by the targeting antibody on the liposome and a particular mRNA in the cell selected by sequence complementarity with the liposome-encapsulated oligomer. Nonencapsulated oligomers are sensitive to nucleases and usually must be administered to cells at high concentrations. Oligomers encapsulated in liposomes resist DNase and are active in amounts 1-2 orders of magnitude lower than for those reported for unencapsulated oligomer sequences.
Leonetti
J P
JP
Laboratoire de Biochimie des Protéines, Université des Sciences et Techniques du Languedoc, Montpellier, France.
Machy
P
P
Degols
G
G
Lebleu
B
B
Leserman
L
L
D015060:1,2-Dipalmitoylphosphatidylcholine; D000818:Animals; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D001483:Base Sequence; D007700:Kinetics; D007739:L Cells; D008081:Liposomes; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D012367:RNA, Viral / Q000235:genetics*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D012367:RNA, Viral; D014764:Viral Proteins; D015060:1,2-Dipalmitoylphosphatidylcholine