Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation

Vigne, Emmanuelle; Dedieu, JF; Brie, A; Gillardeaux, A; Briot, Delphine; Benihoud, Karim; Latta-Mahieu, Martine; Saulnier, Patrick; Perricaudet, Michel; Yeh, Patrice

doi:10.1038/sj.gt.3301845

Cited by 53 publications

(40 citation statements)

References 62 publications

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“…The crucial role played by fiber and knob proteins of the virus in transduction prompts the genetic modification of these proteins. Studies have shown that transduction efficiency of the virus has shown dependency on the length of the fiber protein (Legrand, Spehner et al 1999;Shayakhmetov and Lieber 2000;Vigne, Dedieu et al 2003). Further, complete removal of the knob domain has been established as a way to 54 ablate tropism (Magnusson, Hong et al 2001).…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Nigatu

Vupputuri

Flynn

et al. 2013

Journal of Pharmaceutical Sciences

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Linear low‐density polyethylene (LLDPE), based on butene‐1 or hexene‐1, was irradiated with γ‐rays under vacuum or in the presence of air. The study focused on the influence of the dose rate and the γ‐dose on the thermal properties of LLDPE. Differential scanning calorimetry, thermogravimetric analysis (TGA), and TGA/FTIR techniques were used to address the thermal behavior as a result of γ‐irradiation. During this irradiation, competition between crosslinking and scission reactions, subsequent to oxidation reactions, occurred in the polymeric material, which strongly depends on the experimental conditions. A decrease of the crystallinity for γ‐irradiated samples was observed in particular for samples irradiated under vacuum. This observation may be explained by increased hindrance of segment mobility due to crosslinking reactions that prevent crystal growth. TGA investigations revealed an enhancement of the thermal stability for samples irradiated under vacuum but not for those irradiated in air. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2790–2795, 2006

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Section: Conclusion and Recommendationsmentioning

confidence: 99%

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Nigatu

Vupputuri

Flynn

et al. 2013

Journal of Pharmaceutical Sciences

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“…Initial attempts to detarget the liver have been made by ablating the CAR-and integrin-based interactions (Akiyama et al, 2004;Koizumi et al, 2003;Martin et al, 2003;Nakamura et al, 2003). Also, fiber-shaft modifications have been introduced to eliminate virus interactions with native receptors (Bayo-Puxan et al, 2006;Breidenbach et al, 2004;Nicol et al, 2004;Shayakhmetov et al, 2004;Smith et al, 2003b;Vigne et al, 2003). However, the results are variable.…”

Section: Introductionmentioning

confidence: 99%

Polyinosinic acid enhances delivery of adenovirus vectors in vivo by preventing sequestration in liver macrophages

Haisma

Kamps

et al. 2008

Journal of General Virology

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Adenovirus is among the preferred vectors for gene therapy because of its superior in vivo gene-transfer efficiency. However, upon systemic administration, adenovirus is preferentially sequestered by the liver, resulting in reduced adenovirus-mediated transgene expression in targeted tissues. In the liver, Kupffer cells are responsible for adenovirus degradation and contribute to the inflammatory response. As scavenger receptors present on Kupffer cells are responsible for the elimination of blood-borne pathogens, we investigated the possible implication of these receptors in the clearance of the adenovirus vector. Polyinosinic acid [poly(I)], a scavenger receptor A ligand, was analysed for its capability to inhibit adenovirus uptake specifically in macrophages. In in vitro studies, the addition of poly(I) before virus infection resulted in a specific inhibition of adenovirus-induced gene expression in a J774 macrophage cell line and in primary Kupffer cells. In in vivo experiments, pre-administration of poly(I) caused a 10-fold transient increase in the number of adenovirus particles circulating in the blood. As a consequence, transgene expression levels measured in different tissues were enhanced (by 5- to 15-fold) compared with those in animals that did not receive poly(I). Finally, necrosis of Kupffer cells, which normally occurs as a consequence of systemic adenovirus administration, was prevented by the use of poly(I). No toxicity, as measured by liver-enzyme levels, was observed after poly(I) treatment. From our data, we conclude that poly(I) can prevent adenovirus sequestration by liver macrophages. These results imply that, by inhibiting adenovirus uptake by Kupffer cells, it is possible to reduce the dose of the viral vector to diminish the liver-toxicity effect and to improve the level of transgene expression in target tissues. In systemic gene-therapy applications, this will have great impact on the development of targeted adenoviral vectors.

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“…[40][41][42][43][44] These data notwithstanding, work by several groups has implicated the fiber protein as a major structural determinant of liver tropism in vivo (reviewed by Nicklin et al 45 ). For example, shortening of the native fiber shaft domain of the Ad5 fiber 46 or replacement of the Ad5 shaft with the short Ad3 shaft domain 47 was shown to attenuate liver uptake in vivo following intravenous delivery. In related work, Smith et al 48 These efforts serve to highlight the complexity of vector/host interplay, and have identified important genetic modifications that have important practical implications for designing safer and more effective Adbased vectors for clinical applications.…”

Section: Transductional Targeting Of Admentioning

confidence: 99%

Transductional targeting of adenovirus vectors for gene therapy

2006

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Genetic manipulations of adenovirus type 5 fiber resulting in liver tropism attenuation

Cited by 53 publications

References 62 publications

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Evaluation of Cell-Penetrating Peptide/Adenovirus Particles for Transduction of CAR-Negative Cells

Polyinosinic acid enhances delivery of adenovirus vectors in vivo by preventing sequestration in liver macrophages

Transductional targeting of adenovirus vectors for gene therapy

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