Incorporation of adenovirus into a ligand-based DNA carrier system results in retention of original receptor specificity and enhances targeted gene expression

Wu, George Y.; Zhan, Peili; Sze, Lynette; Rosenberg, Arielle R.; Wu, Catherine H.

doi:10.1016/s0021-9258(19)78158-7

Cited by 86 publications

(8 citation statements)

References 29 publications

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“…The use of low-molecular weight components as shown by Gottschalk and colleagues and in this paper is an alternative to the use of cationic polymers. In the past, positively charged polylysine and dendritic polymers, which possess amine termini, have been studied to that end (Wagner et al, 1991;Haensler & Szoka, 1993;Wu et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Polylysine alone has a marginal ability to transfect cells but has been successfully used in conjunction with receptor ligands such as transferrin (Wagner et al, 1991), AsOR (Wu & Wu, 1987), or antibodies (Ferkol et al, 1995). Although polylysine possesses some endosomal-destabilizing ability, the membranedestabilizing capability of polycations has been increased using either inactive adenoviral particles (Curiel et al, 1991;Wagner et al, 1992a,b;Wu et al, 1994;Kremer & Perricaudet, 1995), influenza fusion peptides (Plank et al, 1994;Wagner et al, 1992a,b), or GALA (Haensler & Szoka, 1993). These high-molecular weight cationic polymers are effective at mediating transfection of reporter genes to cells in culture and in ViVo but are polydisperse, require several components, and induce an immune response (Wu & Wu, 1988a,b;Perales et al, 1994;Ferkol et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers

et al. 1997

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We have designed a cationic amphipathic peptide, KALA (WEAKLAKALAKALAKHLAKALAKALKACEA), that binds to DNA, destabilizes membranes, and mediates DNA transfection. KALA undergoes a pH-dependent random coil to amphipathic alpha-helical conformational change as the pH is increased from 5.0 to 7.5. One face displays hydrophobic leucine residues, and the opposite face displays hydrophilic lysine residues. KALA-mediated release of entrapped aqueous contents from neutral and negatively charged liposomes increases with increasing helical content. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gel electrophoresis. It displaces 50% of ethidium bromide from DNA at a charge ratio (+/-) of 0.9/1. In cultured cells, KALA assists oligonucleotide nuclear delivery when complexes are prepared at a 10/1 (+/-) charge ratio. KALA/DNA (10/1)(+/-) complexes mediate transfection of a variety of cell lines. The KALA sequence provides a starting point for a family of peptides that incorporate other functions to improve DNA delivery systems.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers

et al. 1997

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“…Complexes of PLL derivatives with DNA have been shown to be useful for delivering DNA into a cell. 14 Cross-linked PLL gel derivatives have been used as a biodegradable matrix. 15 PLL forms unique conformations in solution, such as R-helix and β-sheet structures, and it is easy to detect a conformational change in PLL by circular dichroism (cd).…”

Section: Introductionmentioning

confidence: 99%

“…PLL has been widely used not only in basic studies but also in biotechnological and pharmaceutical applications. Complexes of PLL derivatives with DNA have been shown to be useful for delivering DNA into a cell .…”

Section: Introductionmentioning

confidence: 99%

Self-Association of Cholesteryl-Bearing Poly(l-lysine) in Water and Control of Its Secondary Structure by Host−Guest Interaction with Cyclodextrin

et al. 2000

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A cholesteryl-bearing poly(l-lysine) (CHPLL) was synthesized by the condensation reaction of cholesteryl N-(6-isocyanatehexyl) carbamate with poly(l-lysine) (PLL). Sonicated samples of CHPLLs, which were substituted by 0.8, 3.4, and 5.4 cholesteryl groups per 100 lysine units, gave a single peak after sufficient ultrasonication by high-performance liquid column chromatography. The particle sizes (RG) and aggregation numbers (N), which were determined by static light scattering, increased with an increase in the DS of cholesterol in CHPLL (R G = 16−22 nm, N = 1.3−4.2). These CHPLLs form an α-helical structure at a lower pH compared to the parent PLL by circular dichroism spectroscopy. The partial modification of PLL by hydrophobic cholesteryl groups leads to the formation of hydrogel nanoparticles by their self-association, and this induces the α-helical structure of PLL. This α-helicity can be controlled by the degree of substitution of cholesteryl groups. The helical content of CHPLL decreased upon the addition of β-cyclodextrins, which were complexed with cholesteryl groups and reached a value similar to that of unmodified PLL. The secondary structure of CHPLL was controlled by host−guest interaction with cyclodextrin.

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“…Many viruses have evolved mechanisms to escape the degradative endosomal-lysosomal pathway. We and others have taken advantage of the endosomolytic property of whole viruses such as adenoviruses ( − ), rhinoviruses (), or short synthetic fusogenic peptides derived from Influenza Virus hemagglutinin ( − ) to enhance DNA escape from endocytotic vesicles and augment gene expression after receptor-mediated gene transfer in vitro. The coadministration of endosomolytic viral particles, like adenoviruses, showed impressive enhancement of gene expression in vitro ().…”

Section: Discussionmentioning

confidence: 99%

Multicomponent DNA Carrier with a Vesicular Stomatitis Virus G-Peptide Greatly Enhances Liver-Targeted Gene Expression in Mice

Schuster

Walton

et al. 1999

Bioconjugate Chem.

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Genes can be targeted to hepatocytes in vitro and in vivo by the use of asialoorosomucoid-polylysine conjugates. After systemic application, this nonviral vector is recognized by highly selective asialoglycoprotein (AsGP) receptors on the sinusoidal liver cell membrane and is taken up via receptor-mediated endocytosis. As most of the DNA is rapidly transferred to lysosomes where it is degraded, transfection efficiency is low and gene expression transient. To address this problem, we incorporated a pH-dependent synthetic hemolytic peptide derived of the G-protein of Vesicular Stomatitis Virus (VSV) into the gene transfer system, to increase endosomal escape of internalized DNA. The multicomponent carrier binds DNA in a nondamaging way, is still recognized by the AsGP receptor, and is targeted to the liver in vivo. Injection of DNA complexes containing a luciferase marker gene resulted in luciferase expression of 29 000 pg/g liver which corresponded to an increase of a factor of 10(3) overexpression after injection of DNA complexes without endosomolytic peptide. Furthermore, the amount of intact transgene within isolated liver cell nuclei was increased by a factor of 10(1)-10(2) by the use of the multicomponent carriers. These results demonstrate that incorporation of a hemolytic peptide into a nonviral vector can greatly increase gene expression while retaining cell type targetability in vivo.

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Incorporation of adenovirus into a ligand-based DNA carrier system results in retention of original receptor specificity and enhances targeted gene expression

Cited by 86 publications

References 29 publications

Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers

Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers

Self-Association of Cholesteryl-Bearing Poly(l-lysine) in Water and Control of Its Secondary Structure by Host−Guest Interaction with Cyclodextrin

Multicomponent DNA Carrier with a Vesicular Stomatitis Virus G-Peptide Greatly Enhances Liver-Targeted Gene Expression in Mice

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