Development of an in vivo adeno-associated virus-mediated siRNA approach to knockdown tyrosine hydroxylase in the lateral retrochiasmatic area of the ovine brain

Dufourny, Laurence; Migaud, Martine; Thiéry, Jean‐Claude; Malpaux, Benoît

doi:10.1016/j.jneumeth.2007.12.018

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…A third member of this class of G-protein-coupled receptors (GPCRs), Mel1c, is known to be functionally present in low vertebrates, reptiles and birds. Only recently has it become clear that the well-known melatonin-related orphan receptor (G-protein-coupled receptor 50, GPR50) [55] is the mammalian ortholog of Mel1c [56]. …”

Section: Membrane Melatonin Receptors Of the Pancreatic β-Cellmentioning

confidence: 99%

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Peschke

Bähr

Mühlbauer

2013

IJMS

141

126

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The pineal hormone melatonin exerts its influence in the periphery through activation of two specific trans-membrane receptors: MT1 and MT2. Both isoforms are expressed in the islet of Langerhans and are involved in the modulation of insulin secretion from β-cells and in glucagon secretion from α-cells. De-synchrony of receptor signaling may lead to the development of type 2 diabetes. This notion has recently been supported by genome-wide association studies identifying particularly the MT2 as a risk factor for this rapidly spreading metabolic disturbance. Since melatonin is secreted in a clearly diurnal fashion, it is safe to assume that it also has a diurnal impact on the blood-glucose-regulating function of the islet. This factor has hitherto been underestimated; the disruption of diurnal signaling within the islet may be one of the most important mechanisms leading to metabolic disturbances. The study of melatonin–insulin interactions in diabetic rat models has revealed an inverse relationship: an increase in melatonin levels leads to a down-regulation of insulin secretion and vice versa. Elucidation of the possible inverse interrelationship in man may open new avenues in the therapy of diabetes.

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Section: Membrane Melatonin Receptors Of the Pancreatic β-Cellmentioning

confidence: 99%

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Peschke

Bähr

Mühlbauer

2013

IJMS

141

126

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“…Only one previous study has tested viral gene transfer in sheep, targeting RNA interference to the hypothalamus using AAV vectors (Dufourny et al, 2008). In addition to utility in the naturally occurring genetic models of NCL developed in sheep (Tammen et al, 2006;Frugier et al, 2008), their similar brain structure and size to humans makes them useful as large-animal models in other diseases.…”

mentioning

confidence: 99%

Lentiviral-Mediated Gene Transfer to the Sheep Brain: Implications for Gene Therapy in Batten Disease

Linterman

Palmer²,

Kay³

et al. 2011

Human Gene Therapy

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The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are inherited neurodegenerative lysosomal storage diseases with common clinical features of blindness and seizures culminating in premature death. Gene-therapy strategies for these diseases depend on whether the missing activity is a secreted lysosomal protein taken up by neighboring cells, or an intramembrane protein that requires careful targeting. Therapies are best developed in animal models with large complex human-like brains. Lentiviral-mediated gene delivery to neural cell cultures from normal sheep and sheep affected with an NCL resulted in green fluorescent protein (GFP) expression in neurons and neuroblasts, more efficiently than in astrocytes. Similar transgene expression was obtained from two constitutive promoters, the viral MND promoter and the human EF1α promoter. In vivo studies showed stable and persistent GFP expression throughout the cell bodies, axons, and dendrites from intracortical injections and indicated ependymal and subependymal transduction. The sheep showed no ill effects from the injections. These data support continuing gene-therapy trials in the sheep models of Batten disease.

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“…Several reports have established that recombinant AAV is capable of expressing siRNA inside cells. It is noted that, AAVmediated RNAi can introduce a safe, long-term gene inhibition in mammalian cells (Tomar et al, 2003;Han et al, 2007;Pinkenburg et al, 2004;Machida et al, 2006;Dufourny et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effective inhibition of specific gene by adeno-associated virus (AAV)-mediated expression of small interfering RNA

Yin¹,

Zhang²,

Yang³

et al. 2011

Afr. J. Biotechnol.

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RNA-interference is the mechanism of sequence-specific, post-transcriptional gene silencing, initiated by small interfering RNA (siRNA), homologous to the gene being suppressed. Several techniques are utilized to transfer siRNA into cultured cells or animal models, while every method has advantages and disadvantages. In this study, a siRNA expression recombinant adeno-associated virus (AAV) was established by inserting H1 promoter into transfer plasmid of AAV Helper-Free system. To perform functional tests on siRNA, which was expressed by the viral vector, recombinant AAVs, coding for siRNA against exogenous gene, EGFP, and endogenous gene, p53, were established and added into HEK293 cells, respectively. The results proved the expression of EGFP and p53 in cells were definitely suppressed at 72 h post-infection, which suggested that the H1 promoter, inserted into the recombinant AAV, could express siRNA in mammalian cells and this siRNA delivery system could be used for longterm gene silencing.

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Development of an in vivo adeno-associated virus-mediated siRNA approach to knockdown tyrosine hydroxylase in the lateral retrochiasmatic area of the ovine brain

Cited by 7 publications

References 36 publications

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Melatonin and Pancreatic Islets: Interrelationships between Melatonin, Insulin and Glucagon

Lentiviral-Mediated Gene Transfer to the Sheep Brain: Implications for Gene Therapy in Batten Disease

Effective inhibition of specific gene by adeno-associated virus (AAV)-mediated expression of small interfering RNA

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