Transfer of a foreign gene into the brain using adenovirus vectors

Akli, Said; Caillaud, Catherine; Vigne, Emmanuelle; Stratford-Perricaudet, Leslie D.; Poënaru, Livia; Perricaudet, Michel; Kahn, Axel; Peschanski, Marc

doi:10.1038/ng0393-224

Cited by 529 publications

(237 citation statements)

References 15 publications

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“…11 Adenoviral vectors have several attractive properties as vehicles of gene transfer into CNS, [12][13][14] although it has become apparent that adenoviral vectors are immunogenic and can induce cytopathic effects. 15,16 They can be prepared in high titer, can be used safely for human vaccination, and can accommodate relatively large gene inserts; they are particularly useful for infection and expression in terminally differentiated non-dividing cells, such as neurons.…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice

et al. 2001

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We investigated genes expression by retrograde axonal transport of replication-defective adenoviruses carrying genes for LacZ (AdLacZ) and Bcl-2 in motor neurons of transgenic mice expressing mutant human Cu/Zn superoxide dismutase (SOD1) gene containing a substitution of alanine for glycine at position 93. We found that intramuscular injection of AdLacZ into the tongue of mutant SOD1 transgenic mice and their wild-type littermates at various ages results in high expression of the transgene and similar time course of expression in hypoglossal cranial nerve nuclei, suggesting no difference in the behavior of the transgene expression between the two groups. Subsequently, we employed a molecular switching cassette for Bcl-2 designed to express Bcl-2 by Cre-loxP recombination using adenoviral vectors, and examined the COS7 and primary neuronal cells with the mutant SOD1 gene. The overexpression of Bcl-2 in

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Section: Introductionmentioning

confidence: 99%

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice

et al. 2001

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“…The recombinant version of Ad can transduce both mitotic and post-mitotic cells. In the CNS, Ad transduces both neurons and glia (Akli et al, 1993) and rAd supports high levels of transgene expression (Bohn et al, 1999;Gerdes et al, 2000). The wild-type adenoviral genome is composed of two inverted terminal repeats that are required for replication, a packaging signal, early genes and late genes.…”

Section: Recombinant Adenovirus (Rad)mentioning

confidence: 99%

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

Mandel

Bürger

Snyder

2008

Experimental Neurology

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Because Parkinson's disease is a progressive degenerative disorder that is mainly confined to the basal ganglia, gene transfer to deliver therapeutic molecules is an attractive treatment avenue. The present review focuses on direct in vivo gene transfer vectors that have been developed to a degree that they have been successfully used in animal model of Parkinson's disease. Accordingly, the properties of recombinant adenovirus, recombinant adeno-associated virus, herpes simplex virus, and lentivirus are described and contrasted. In order for viral vectors to be developed into clinical grade reagents, they must be manufactured and tested to precise regulatory standards. Indeed, clinical lots of viral vectors can be produced in compliance with current Good Manufacturing Practices (cGMPs) regulations using industry accepted manufacturing methodologies, manufacturing controls, and quality systems. The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration.

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“…Several groups have demonstrated that pre-delivery of GDNF into rat brain using an adenoviral vector, prior to a 6-hydroxydopamine (6-OHDA) lesion can dramatically reduce the cell loss and/or behavioral deficits induced by the lesion [1,3,14,25]. Similar studies using adeno-associated viruses also report sparing of dopamine neurones from the toxin [6,13,22,24,31].…”

Section: Introductionmentioning

confidence: 99%

In vivo transgene expression from an adenoviral vector is altered following a 6-OHDA lesion of the dopamine system

Torres

Monville

Löwenstein

et al. 2005

Molecular Brain Research

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We have investigated the in vivo dynamics of an adenovirus-based, LacZ expressing vector, RAd36, at different doses, when injected unilaterally into the corpus striatum of normal rats. We have further investigated the characteristics of this vector in the presence of a 6-OHDA lesion of the nigrostriatal pathway. The dopamine-depleting lesion had an effect on both the number and the distribution of cells transduced by the adenoviral vector. The lesioned side of the brain contained significantly greater numbers of β-galactosidase positive cells than the unlesioned side at 3 days, 1 week and 4 weeks post-injection and the distribution of transduced cells was altered by the presence of a dopamine lesion. We conclude that the increased levels of transgene expression seen in the lesioned hemisphere are due to a change in the diffusion characteristics of the injected vector in the lesioned hemisphere. These results indicate that, when investigating the use of virus-based vectors, ultimately for use in gene therapies in the CNS, the in vivo dynamics of the vector need to be assessed not only in the normal brain, but also in the pathological brain state such as animal models of target diseases.

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Transfer of a foreign gene into the brain using adenovirus vectors

Cited by 529 publications

References 15 publications

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice

Viral vectors for in vivo gene transfer in Parkinson's disease: Properties and clinical grade production

In vivo transgene expression from an adenoviral vector is altered following a 6-OHDA lesion of the dopamine system

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