Localized adenovirus gene delivery using antiviral IgG complexation

Levy, Robert J.; Song, Cunxian; Tallapragada, Sruthi; DeFelice, Suzanne; Hinson, J. Travis; Vyavahare, Narendra R.; Connolly, JM; Ryan, Kevin; Li, Q

doi:10.1038/sj.gt.3301452

Cited by 59 publications

(67 citation statements)

References 35 publications

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“…In substrate-mediated delivery, DNA is immobilized to a substrate for delivery to cells that adhere to the substrate [8,9]. Efficient delivery of DNA complexes from a surface is dependent on balancing the interactions between the substrate and the complexes.…”

Section: Discussionmentioning

confidence: 99%

“…Specific interactions can be introduced through complementary functional groups on the vector and surface, such as antigen-antibody or biotin-avidin [8,9]. The effective affinity of the vector for the substrate is determined by the strength of the specific interactions, which may also be influenced by environmental conditions (e.g., ionic strength, pH), binding-induced conformational changes, or vector unpacking.…”

Section: Introductionmentioning

confidence: 99%

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Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

2005

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Gene transfer has many potential applications in basic and applied sciences. In vitro, DNA delivery can be enhanced by increasing the concentration of DNA in the cellular microenvironment through immobilization of DNA to a substrate that supports cell adhesion. Substrate-mediated delivery describes the immobilization of DNA, complexed with cationic lipids or polymers, to a biomaterial or substrate. As surface properties are critical to the efficiency of the surface delivery approach, selfassembled monolayers (SAMs) of alkanethiols on gold were used to correlate surface chemistry of the substrate to binding, release, and transfection of non-specifically immobilized complexes. Surface hydrophobicity and ionization were found to mediate both DNA complex immobilization and transfection, but had no effect on complex release. Additionally, SAMs were used in conjunction with soft lithographic techniques to imprint substrates with specific patterns, resulting in patterned DNA complex deposition and transfection, with transfection efficiencies in the patterns nearing 40%. Controlling the interactions between complexes and substrates, with the potential for patterned delivery, can be used to locally enhance or regulate gene transfer, with applications to tissue engineering scaffolds and transfected cell arrays.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

2005

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“…[1][2][3] Furthermore, there have been no reports of gene delivery systems for administering gene vectors to heart valve leaflets. However, investigations of gene delivery stents by our group [4][5][6][7] and others indicate a potentially more productive approach. In these studies, either plasmid DNA 4 or replication defective adenoviruses [5][6][7] have been incorporated onto the surfaces of balloon expandable stainless-steel stents to administer gene vectors via arterial wall delivery at the time of stent angioplasty.…”

Section: Introductionmentioning

confidence: 99%

“…However, investigations of gene delivery stents by our group [4][5][6][7] and others indicate a potentially more productive approach. In these studies, either plasmid DNA 4 or replication defective adenoviruses [5][6][7] have been incorporated onto the surfaces of balloon expandable stainless-steel stents to administer gene vectors via arterial wall delivery at the time of stent angioplasty. 4,5 Our group's adenoviral vector studies have focused on covalently linking anti-adenoviral antibodies to stent coatings in order to deliver adenoviruses using a vector tethering mechanism.…”

Section: Introductionmentioning

confidence: 99%

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

et al. 2003

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The present study investigated a novel approach for gene therapy of heart valve disease and vascular disorders. We formulated and characterized implantable polyurethane films that could also function as gene delivery systems through the surface attachment of replication defective adenoviruses using an anti-adenovirus antibody tethering mechanism. Our hypothesis was that we could achieve site-specific gene delivery to cells interacting with these polyurethane implants, and thereby demonstrate the potential for intravascular devices that could also function as gene delivery platforms for therapeutic vectors. Previous research by our group has demonstrated that polyurethane elastomers can be derivatized post-polymerization through a series of chemical reactions activating the hard segment amide groups with alkyl bromine residues, which can enable a wide variety of subsequent chemical modifications. Furthermore, prior research by our group investigating gene delivery intravascular stents has shown that collagen-coated balloon expandable stents can be configured with anti-adenovirus antibodies via thiol-based chemistry, and can then tether adenoviral vectors at doses that lead to high levels of localized arterial neointima expression, but with virtually no distal spread of vector. Thus, we sought to create two-device configurations for our investigations building on this previous research. (1) Polyurethane films coated with Type I collagen were thiol activated to permit covalent attachment of anti-adenovirus antibodies to enable gene delivery via vector tethering. (2) We also formulated polyurethane films with direct covalent attachment of anti-adenovirus antibodies to polyurethane hard segments derivatized with alkyl-thiol groups, thereby also enabling tethering of replication-defective adenoviruses. Both formulations demonstrated highly localized and efficient transduction in cell culture studies with rat arterial smooth muscle cells. In vivo experiments with collagen-coated polyurethane films investigated an abdominal aorta implant model in pigs using a button configuration that simulated the blood contacting environment of a vascular graft. One week explants of the collagen-coated polyurethane films demonstrated 14.372.5% of neointimal cells on the surface of the implant transduced with green fluorescent protein -adenovirus (AdGFP) vector loadings of 1 Â 10 8 PFU. PCR studies demonstrated no detectable vector DNA in blood or distal organs. Similarly, polyurethane films with direct attachment of antivector antibodies to the surface were used in sheep pulmonary valve leaflet replacement studies, simulating the blood contacting environment of a prosthetic heart valve cusp. Polyurethane films with antibody tethered AdGFP vector (10 8 PFU) demonstrated 25.175.7% of attached cells transduced in these 1 week studies, with no detectable vector DNA in blood or distal organs. In vivo GFP expression was confirmed with immunohistochemistry. It is concluded that site-specific intravascular delivery of adenoviral vectors for g...

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“…This chapter includes protocols for one lipid-based transfection reagent (Lipofectamine 2000) and one polymer-based transfection reagent (PEI). However, surface-mediated delivery has also been accomplished with jet-PEI (3, 16), Lipofectamine LTX (35), FugeneHD (Rocher) (unpublished results), and Effectene (Qiagen) (35), as well as viral vectors (15,(38)(39)(40)(41)(42)(43). The encapsulation of lipoplexes and jetPEI/DNA polyplexes into hydrogel scaffolds has also been possible using a similar protocol (36).…”

Section: Notesmentioning

confidence: 99%

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

Pannier

Segura

2012

Nanotechnology for Nucleic Acid Delivery

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Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. Furthermore, bolus delivery cannot be used in applications where patterning of gene expression is needed. In this chapter, we describe methods that incorporate material surfaces (i.e., surface-mediated delivery) or hydrogel scaffolds (i.e., hydrogel-mediated delivery) to efficiently deliver genes. This chapter includes protocols for surface-mediated DNA delivery focusing on the simplest and most effective methods, which include nonspecific immobilization of DNA complexes (both polymer and lipid vectors) onto serum-coated cell culture polystyrene and self-assembled monolayers of alkanethiols on gold. Also, protocols for the encapsulation of DNA/cationic polymer nanoparticles into hydrogel scaffolds are described, including methods for the encapsulation of low amounts of DNA (<0.2 μg/μL) and high amounts of DNA (>0.2 μg/μL) since incorporation of high amounts of DNA poses significant challenges due to aggregation.

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Localized adenovirus gene delivery using antiviral IgG complexation

Cited by 59 publications

References 35 publications

Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

Substrate-mediated delivery from self-assembled monolayers: Effect of surface ionization, hydrophilicity, and patterning

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

Surface- and Hydrogel-Mediated Delivery of Nucleic Acid Nanoparticles

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