Biomaterial Database

Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides. 1992

G Y Wu, and C H Wu

Department of Medicine, University of Connecticut School of Medicine, Farmington 06030.

A 21-mer oligodeoxynucleotide complementary to the polyadenylation signal for human hepatitis B virus (HBV) was complexed to a soluble DNA-carrier system that is targetable to hepatocytes via asialoglycoprotein receptors present on those cells. A cell line, HepG2 (2.2.15) that possesses asialoglycoprotein receptors and is permanently transfected with hepatitis B virus (ayw subtype) was exposed to complexed antisense DNA or controls. In the presence of complexed antisense DNA, the concentration of hepatitis B surface antigen in medium was 80% lower than controls after 24 h. Furthermore, during the next 6 days, there was no significant increase in surface antigen concentration in the presence of complexed antisense DNA. The inhibition could be effectively blocked by competition with an excess of free asialoglycoprotein. Total protein synthesis remained unchanged by exposure to complexed antisense sequences under identical conditions. In addition, HBV DNA in the medium and cell layers after 24-h exposure to complexed antisense sequences was 80% lower than in controls. The data indicate that antisense oligonucleotides complexed by a soluble DNA-carrier system can be targeted to cells via asialoglycoprotein receptors resulting in specific inhibition of hepatitis B viral gene expression and replication.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D011971	Receptors, Immunologic	Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.	Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D006514	Hepatitis B Surface Antigens	Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.	Australia Antigen,HBsAg,Hepatitis B Surface Antigen,Antigen, Australia
D006515	Hepatitis B virus	The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum.	Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015139	Blotting, Southern	A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.	Southern Blotting,Blot, Southern,Southern Blot
D015967	Gene Expression Regulation, Viral	Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.	Regulation of Gene Expression, Viral,Viral Gene Expression Regulation,Regulation, Gene Expression, Viral
D016373	DNA, Antisense	DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes.	Antisense DNA,Anti-Sense DNA,Anti Sense DNA,DNA, Anti-Sense
D037263	Asialoglycoprotein Receptor	A C-type lectin that is a cell surface receptor for ASIALOGLYCOPROTEINS. It is found primarily in the LIVER where it mediates the endocytosis of serum glycoproteins.	Asialoglycoprotein Receptors,ASGP-R,Asialoorosomucoid Receptor,Asialoorosomucoid Receptors,Asialoorosomucoid-Binding Protein,Hepatic Asialoglycoprotein Receptor,Hepatic Lectin,Liver Carbohydrate-Binding Protein,Receptor, Asialoglycoprotein,Receptor, Asialoorosomucoid,Asialoglycoprotein Receptor, Hepatic,Asialoorosomucoid Binding Protein,Carbohydrate-Binding Protein, Liver,Lectin, Hepatic,Liver Carbohydrate Binding Protein,Receptor, Hepatic Asialoglycoprotein,Receptors, Asialoglycoprotein,Receptors, Asialoorosomucoid