Targeted polynucleotides for inhibition of hepatitis B and C viruses.
OBJECTIVE
To determine whether a combination of cell targeting and sequence recognition of nucleic acids can provide specificity for the inhibition of viral gene expression.


METHODS
Antisense oligonucleotides complexed to a protein-based DNA carrier system were used to target hepatocytes for the inhibition of human hepatitis viral gene expression. The DNA carrier system contained an asialoglycoprotein as a cell-targeting component, which could direct the uptake of complexed DNA specifically to asialoglycoprotein receptors present selectively on the surface of mammalian hepatocytes.


RESULTS
HBV and HCV viral gene expression were substantially and specifically inhibited by use of antisense oligonucleotides complexed to a protein-based DNA carrier system.


CONCLUSIONS
Targeted delivery of nucleic acids by use of receptor-mediated endocytosis can result in inhibition of viral gene expression without host toxicity.
Wu
G Y
GY
Division of Gastroenterology-Hepatology, Department of Medicine, University of Connecticut Health Center, Rm. AM-044, 263 Farmington Avenue, Farmington, CT 06030-1845, USA. wu@nso.uchc.edu
Walton
C M
CM
Wu
C H
CH
D015967:Gene Expression Regulation, Viral / Q000502:physiology; D018390:Gene Targeting; D016174:Hepacivirus / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics; D014162:Transfection
D016376:Oligonucleotides, Antisense