Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter

Navarro, Vincent; Millecamps, Stéphanie; Geoffroy, M; Robert, J; Valín, Álvaro; Mallet, Jacques; Salle, G. Le Gal La

doi:10.1038/sj.gt.3301008

Cited by 57 publications

(35 citation statements)

References 25 publications

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“…17,[20][21][22][23] We have assessed this for up to 3 months after CNS-1 tumor implantation in the survivors after gene therapy using RAd/HSV1-TK plus ganciclovir. The reasons for this are two-fold.…”

Section: Ecorin Plays Different Roles In Regulating Matrixmentioning

confidence: 99%

“…Construction of the RAd/hCMV/b-gal and RAd/hCMV/ HSV1-TK has been described in detail elsewhere. 21,40 To create the shuttle vector pDE1/GFAP/decorin, which was used to generate RAd/GFAP/decorin, a blunted EcoRI human decorin fragment (1780 bp) was cloned into the blunted BamHI site of the pDE1/GFAP. 36 A blunted EcoRI human decorin fragment (1780 bp) was cloned into the blunted BamHI site of pAL119 (pMV35 in Shering et al 40 ) to create the shuttle vector pAL119/decorin which was used to generate RAd/hCMV/decorin.…”

Section: Recombinant Adenovirusesmentioning

confidence: 99%

“…Rats were monitored daily and unwell rats anesthetized, perfused, and fixed, as described previously. 21 …”

Section: Experimental Gliomasmentioning

confidence: 99%

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Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model

et al. 2004

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Given the failure of conventional treatments for glioblastoma, gene therapy has gained interest considerable in recent years. Gliomas are associated with a state of immunosuppression, which appears to be partially mediated by an increase in secretion of transforming growth factor-b (TGF-b) from glioma cells. Decorin, a small proteoglycan which can bind to and inactivate TGF-b, has been successfully used as an antitumor strategy on stably transfected tumor cells and has been shown to cause growth suppression in neoplastic cells of various histological origins. In this paper, we investigated the use of gene therapy to deliver the decorin transgene in a site-specific manner in an experimental model of intracranial gliomas. Our aim was to inhibit the glioma-associated immunosuppressive state, and prolong the survival of tumor-bearing rats.We studied the effects of decorin gene transfer in the rat CNS-1 glioma model. To assess the effect of ectopic expression of decorin on glioma progression in vivo, stably transfected CNS-1 cells expressing decorin were implanted into the brain parenchyma of syngeneic Lewis rats. The rats implanted with CNS-1 cells expressing decorin survived significantly longer than those in the control groups which received CNS-1 cells that did not express decorin (Po.0001). We then investigated whether the survival observed with decorin expressing cells could be mimicked in vivo, using recombinant adenoviruses (RAds) expressing the decorin gene under the control of two different promoters: the human immediate-early cytomegalovirus (h-IE-CMV) and the glial fibrillary acidic protein (GFAP). In vivo results showed that administration of RAd expressing the human decorin under the control of h-IE-CMV promoter has a small, but significant effect in prolonging the survival of experimental tumor bearing rats (Po.0001). Our data indicate that ectopic decorin expression has the potential to slow glioma progression in vivo. Our results also indicate that expression of decorin has to be present in all cells which constitute the intracranial tumor mass for the inhibition of tumor growth and prolongation of the life expectancy of tumor-bearing rats to be effective.

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Section: Ecorin Plays Different Roles In Regulating Matrixmentioning

confidence: 99%

Section: Recombinant Adenovirusesmentioning

confidence: 99%

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Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model

et al. 2004

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“…Adenoviral vectors containing a viral promoter such as the cytomegalovirus (CMV) we employed in this study or Rous sarcoma virus have been shown to have high transcription levels, but to have short-term efficiency of viral promoter suggested by down-regulation of transcription through cellular defense mechanisms. 23 Navarro et al 24 reported that ␤-gal gene expression remained stable for 3. months and was detectable for 6 months after administration of AdLacZ with promoter of neuron-specific enolase. Thus, a promoter we employ should be an important factor for transgene expression.…”

Section: Figure 7 Detection Of Immunoreactivity For Bcl-2 In the Tongmentioning

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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“…3 In addition, a range of novel promoters have been isolated and characterized that confer sustained high level constitutive and tissue specific expression. 4,5 These advances have lead to promising applications for rAAV including novel therapies for disease models in rodents 6,7 and nonhuman primates. 8,9 Translation to the clinic for rAAV is currently limited to diseases in which regulation of the transgenic protein is not critical, for example factor IX in hemophilia, or CFTR in cystic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Insulators coupled to a minimal bidirectional tet cassette for tight regulation of rAAV-mediated gene transfer in the mammalian brain

2001

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Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter

Cited by 57 publications

References 25 publications

Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model

Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model

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

Insulators coupled to a minimal bidirectional tet cassette for tight regulation of rAAV-mediated gene transfer in the mammalian brain

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