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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus type 5 was modified by coupling an asialoglycoprotein-polylysine conjugate to the virus by reactions that activate carbohydrate residues. Wild-type virus modified in this manner had greatly decreased infectivity toward normally susceptible HeLa S3 (asialoglycoprotein receptor (-)) and SK Hep1 (asialoglycoprotein receptor (-)) cells leaving 91 and 86% viable, respectively, after 48 h. However, with Huh 7 (asialoglycoprotein receptor (+)) cells, modified virus retained its infectivity leaving only 19% of cells viable under identical conditions. Modified virus was complexed to DNA in the form of a plasmid, pSVHBV surf, containing the gene for hepatitis B surface antigen as a marker of gene expression. Huh 7, receptor (+), cells treated with modified wild type, and modified replication-defective d1312 virus complexed to DNA raised antigen levels by approximately 13- and 30-fold, respectively, compared with asialoglycoprotein-polylysine DNA complex alone. Competition with a large excess of an asialoglycoprotein blocked the enhancement by more than 95%. Using a beta-galactosidase marker gene, the number of cells transfected by modified virus was found to be 200-fold higher than complex alone. Yet, specificity was retained exclusively for asialoglycoprotein receptor-bearing cells. These data indicate that adenovirus can be chemically modified by coupling ligands resulting in targeted gene expression dictated specifically by receptor recognition of the attached ligand.
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PMID:Incorporation of adenovirus into a ligand-based DNA carrier system results in retention of original receptor specificity and enhances targeted gene expression. 815 85

Ligand-mediated approaches to gene transfer offer an alternative to viral vectors for both in vivo and in vitro applications. Although a significant percentage of the plasmid-based DNA complex is lost to lysosomal degradation following receptor-mediated endocytosis, simultaneous infection with adenovirus has been shown to increase the level of transgene expression [Curiel, Agarwal, Wagner and Cotten (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8850-8854; Wagner, Zatloukal, Cotten, Kirlappos, Mechtler, Curiel and Birnstiel (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6099-6103]. In this study we describe an adenovirus-based ligand complex where the plasmid DNA, polycation-ligand conjugate and adenovirus are contained within a single particle structure. At the core of the transfection particle is a replication-defective recombinant adenovirus encoding a cDNA minigene for human placenta alkaline phosphatase that was chemically modified with poly(L-lysine) (Ad-pLys). Electron microscopy of an adenovirus-based ligand complex formed by successively adding plasmid DNA and an asialo-orosomucoid-poly(L-lysine) conjugate to Ad-pLys revealed structures that appeared as intact viral particles coated with a dense biomolecular layer. Adenovirus-based ligand complexes containing either a luciferase or beta-galactosidase reporter plasmid were shown to efficiently deliver the plasmid transgene to cells that express the hepatic asialoglycoprotein receptor. Furthermore, the poly(L-lysine) modification greatly reduced the infectivity potential of the virus without causing a concomitant loss of augmented gene transfer. As an alternative to infectious virions, incomplete products of viral assembly were also considered as a source for endosomalytic activity. However, these defective virions were unable to significantly enhance plasmid transgene delivery.
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PMID:Biochemical and functional analysis of an adenovirus-based ligand complex for gene transfer. 816 59