TARGETED DELIVERY OF ANTISENSE DNA IN WOODCHUCK HEPATITIS VIRUS-INFECTED WOODCHUCKS

An asialoglycoprotein-based DNA delivery system containing an antisens e oligo DNA against the polyadenylation region and adjacent upstream s equences of woodchuck hepatitis virus (WHV) was prepared, Experimental woodchucks were inoculated neonatally with the woodchuck virus 23 wee ks before initiating the study, and all animals subsequently developed hepatitis as evidenced by the presence of measurable levels of circul ating viral DNA, Animals were injected intravenously (i.v.) with asial oorosomucoid (AsOR)-poly-L-lysine complexes containing 0.1 mg kg(-1) a ntisense DNA for five consecutive days. Levels of surface antigen did not differ substantially between treated and control animals. However, intravenous administration of complexed antisense DNA significantly d ecreased viraemia, as shown by a five- to 10-fold decrease in circulat ing viral DNA 25 days post treatment. The decline lasted for at least 2 weeks, after which there was a gradual increase in DNA levels. Antis ense DNA alone or a complex containing a random oligo DNA of the same size and linkage failed to have any significant effect on viral DNA le vels. We conclude that antisense oligo DNA can be targeted to the live r in vivo, resulting in a substantial and prolonged decrease in viral DNA levels in WHV-infected woodchucks.