Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Brunetti‐Pierri, Nicola; Ng, Philip

doi:10.1038/gt.2008.14

Cited by 73 publications

(52 citation statements)

References 52 publications

(70 reference statements)

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“…This Ad-based vector has all viral coding sequences removed, leaving only sequences for packaging and vector propagation. 10 HDAd vectors derived from human Ad serotype 5 preferentially transduce the liver, where infection efficacy rates may approach 100%. 11 Baboons and mice given a single dose of an HDAd vector had appreciable hepatic transgene expression, lasting 1-2.5 years.…”

Section: Introductionmentioning

confidence: 99%

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia

et al. 2011

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Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia.

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Section: Introductionmentioning

confidence: 99%

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia

et al. 2011

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“…[81][82][83] The most recent generation of adenoviral vectors allows the use of longer tissue-specific or regulatable promoters that can modulate the immune response. 84 Capsid modification with polyethylene glycol (PEGylation) reduced the innate immune response of fully deleted vectors in the periphery and therefore such modification also has potential for reducing the immune response in the CNS.…”

Section: Novel Viral Vectors Further Reduce Immunological Riskmentioning

confidence: 99%

Progress and prospects: Immunobiology of gene therapy for neurodegenerative disease: prospects and risks

McMenamin

Wood

2010

Gene Ther

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Gene therapy for neurological, and in particular neurodegenerative, disease is now a reality. A number of early phase clinical trials have been completed and several are currently in progress. In view of this, it is critically important to evaluate the immunological risk associated with neurological gene therapy, which has clear implications for trial safety and efficacy. Moreover, it is imperative in particular to identify factors indicating potential high risk. In the light of recent advances in understanding immune regulation in the central nervous system (CNS) and with the continued development of new gene delivery vectors, this review critically assesses the current knowledge of immunobiology within the CNS in terms of likely immunological risk pertaining to viral vectors and gene therapy applications for neurodegenerative disease.

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“…However, continued trials for viruses packaged into HEK 293 cells or local application of small particles into limited areas, as was performed in our study, have successfully reduced the risks of infection and other definitive risk factors. 11,12 As described above, a further study should be performed to investigate the safety of combination therapy of MDR1 shRNA therapy and hNIS radioiodine gene therapy using the adenoviral system.…”

Section: Discussionmentioning

confidence: 99%

“…An adenoviral vector is the major delivery system commonly used for gene therapy in vivo. 11,12 The use of an adenoviral vector system has been reported to have several beneficial features as compared with other viral vector systems, such as efficient transfection in various cells including both quiescent and dividing cells, and high level expression of the gene of interest by the use of a cytomegalovirus promoter during the short term.…”

Section: Introductionmentioning

confidence: 99%

Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

et al. 2010

Cancer Gene Ther

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Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1-and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed b-galactrosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes.

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Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors

Cited by 73 publications

References 52 publications

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia

Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia

Progress and prospects: Immunobiology of gene therapy for neurodegenerative disease: prospects and risks

Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

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