Antibody-targeted liposomes containing oligodeoxyribonucleotides complementary to viral RNA selectively inhibit viral replication.

Abstract

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.