Polycations and cationic lipids enhance adenovirus transduction and transgene expression in tumor cells

Clark, Paul; Stopeck, Alison; Brailey, Jacqueline L.; Wang, Qing; McArthur, James G.; Finer, Mitch; Hersh, Evan M.

doi:10.1038/sj.cgt.7700074

Cited by 32 publications

(21 citation statements)

References 15 publications

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“…In previous studies, it was shown that polycations improved binding and uptake of standard Ad5-based vectors (15,33,36,40). In these reports, a number of hypotheses were proposed to explain this phenomenon, including polycation-mediated increase in cell permeability, changes in cellular metabolism or receptor expression, or neutralization of serum factors that interfere with Ad binding.…”

Section: Construction Of Chimeric Ad Vectorsmentioning

confidence: 98%

Dependence of Adenovirus Infectivity on Length of the Fiber Shaft Domain

Shayakhmetov

Lieber

2000

J Virol

178

166

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One of the objectives in adenovirus (Ad) vector development is to target gene delivery to specific cell types. Major attention has been given to modification of the Ad fiber knob, which is thought to determine virus tropism. However, among the human Ad serotypes with different tissue tropisms, not only the knob but also the length of the fiber shaft domain varies significantly. In this study we attempted to delineate the role of fiber length in coxsackievirus-adenovirus receptor (CAR)-and non-CAR-mediated infection. A series of Ad serotype 5 (Ad5) capsid-based vectors containing long or short fibers with knob domains derived from Ad5, Ad9, or Ad35 was constructed and tested in adsorption, internalization, and transduction studies. For Ad5 or Ad9 knobpossessing vectors, a long-shafted fiber was critical for efficient adsorption/internalization and transduction of CAR/␣v integrin-expressing cells. Ad5 capids containing short CAR-recognizing fibers were affected in cell adsorption and infection. In contrast, for the chimeric vectors possessing Ad35 knobs, which enter cells by a CAR/␣v integrin-independent pathway, fiber shaft length had no significant influence on binding or infectibility on tested cells. The weak attachment of short-shafted Ad5 or Ad9 knob-possessing vectors seems to be causally associated with a charge-dependent repulsion between Ad5 capsid and acidic cell surface proteins. The differences between short-and long-shafted vectors in attachment or infection were abrogated by preincubation of cells with polycations. This study demonstrates that the fiber-CAR interaction is not the sole determinant for tropism of Ad vectors containing chimeric fibers. CAR-and ␣v integrin-mediated infections are influenced by other factors, including the length of the fiber shaft.Most recombinant adenovirus (Ad) vectors currently used for in vitro and in vivo gene transfer are based on serotype 5 (Ad5). Efficient transduction with these vectors requires the presence of appropriate cell receptors for binding and/or internalization. High-affinity binding of Ad5 is mediated through the coxsackievirus and Ad receptor (CAR) (6, 7, 68). Ad5 internalization requires an additional interaction of RGD motifs on the penton base with ␣v␤3 and/or ␣v␤5 integrins on the cell surface (32,39,48,71).Safety and efficacy of in vivo applications of Ad vectors require targeting to specific tissues, which is precluded by the widespread distribution of CAR and ␣v integrins. On the other hand, a number of tissues, which represent important targets for gene therapy, are refractory to Ad5 infection due to the lack of these receptors (11,64,70,73). Therefore, modification of tropism is one of the central tasks in Ad vector development. One strategy to retarget Ad5 vectors involves complexing the Ad capsid with bispecific antibodies (18, 70) or peptide ligands (17, 58). Another approach is genetic modification of the Ad5 fiber knob (43), which is aimed toward the incorporation of specific peptide ligands into the Ad5 knob with simultaneous abrogat...

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Section: Construction Of Chimeric Ad Vectorsmentioning

confidence: 98%

Dependence of Adenovirus Infectivity on Length of the Fiber Shaft Domain

Shayakhmetov

Lieber

2000

J Virol

178

166

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“…Several studies have shown that complexation of Ad vectors with cationic lipids/polymers improves infection of a number of cell lines in vitro [11][12][13][14][15][16] and airway epithelial cells following intratracheal instillation in mice. 12 To Figure 1 Gene Figure 3 shows gene expression in liver and lung 3 days following injection of various amounts of AdCMVLuc, alone or following preinjection of DOTAP:cholesterol liposomes (0.9 mol/mouse).…”

Section: Premixing Of Cationic Liposomes With Ad Vectors Leads To Decmentioning

confidence: 99%

“…[11][12][13][14][15][16] Complexation of Ad vectors with cationic liposomes has also been shown to enhance the infection of airway epithelial cells upon instillation into mouse trachea. 12 Cationic liposomes enhance Ad vectormediated infection mainly by improving the cellular uptake.…”

Section: Figure 8 Cytokine Levels In Mouse Serum (A) or Bronchoalveolmentioning

confidence: 99%

Redirecting adenovirus to pulmonary endothelium by cationic liposomes

Ma¹,

Zhang²,

Wilson³

et al. 2002

Gene Ther

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“…[6][7][8] One strategy for obtaining CAR-independent entry in Ad5-resistant cells is to make noncovalent complexes of adenovirus (Ad) with cationic agents. [9][10][11][12][13][14][15][16] The cationic components can associate with the Ad particles due to the net negative viral surface charge, and hence, the attachment to the negatively charged cell membrane is facilitated. This method enables potent gene delivery via CAR-independent cell infection, demonstrating that the interaction with the primary receptor is not crucial for cellular entry.…”

Section: Introductionmentioning

confidence: 99%

“…9,12 Increased viral uptake and transgene expression due to the use of cationic polymers has been reported in airway epithelia in vitro 9 and in vivo, 11 as well as in cultured smooth muscle cells 12 and in tumor cells. 13 As the fiber-CAR interaction largely determines cell tropism for native Ad5, fiberless particles have been constructed to abrogate all interaction with the primary receptor. 17,18 The penton base of such particles is competent to interact with cellular integrins, and the particles are capable of infecting cells trough a CARindependent pathway although with a severely reduced infectivity.…”

Section: Introductionmentioning

confidence: 99%