Improved neurotensin-vector-mediated gene transfer by the coupling of hemagglutinin HA2 fusogenic peptide and Vp1 SV40 nuclear localization signal

Navarro-Quiroga, Iván; González-Barrios, Juan Antonio; Barron-Moreno, Fernando; González-Bernal, Vı́ctor; Martinez–Arguelles, Daniel B.; Martínez‐Fong, Daniel

doi:10.1016/s0169-328x(02)00396-0

Cited by 46 publications

(117 citation statements)

References 51 publications

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“…6 This peptide is used to prevent pDNA degradation in the acidic endosomes. 7,8 The KP (20 amino acids) is the potent nuclear location signal of the SV40 capsid protein Vp1 9 that is used in the NT-polyplex for an efficient targeting of pDNA to the cell nucleus. 8 These features of the NTpolyplex lead to an efficient gene transfection (450%) in cultured cells and in animals 3,8 and a long-lasting transgene expression in animals (43 months).…”

Section: Introductionmentioning

confidence: 99%

“…7,8 The KP (20 amino acids) is the potent nuclear location signal of the SV40 capsid protein Vp1 9 that is used in the NT-polyplex for an efficient targeting of pDNA to the cell nucleus. 8 These features of the NTpolyplex lead to an efficient gene transfection (450%) in cultured cells and in animals 3,8 and a long-lasting transgene expression in animals (43 months). 8 The first use of the NT-polyplex in gene therapy was the transfection of the GDNF gene in nigral dopaminergic neurons in an animal model of Parkinson's disease, because these neurons express 4,10 and internalize NTSR1.…”

Section: Introductionmentioning

confidence: 99%

“…8 These features of the NTpolyplex lead to an efficient gene transfection (450%) in cultured cells and in animals 3,8 and a long-lasting transgene expression in animals (43 months). 8 The first use of the NT-polyplex in gene therapy was the transfection of the GDNF gene in nigral dopaminergic neurons in an animal model of Parkinson's disease, because these neurons express 4,10 and internalize NTSR1. 5,8,11 The efficacy of the NT-polyplex is supported by the morphological and functional recovery from dopaminergic neurodegeneration in experimental hemiparkinsonism.…”

Section: Introductionmentioning

confidence: 99%

“…8 The first use of the NT-polyplex in gene therapy was the transfection of the GDNF gene in nigral dopaminergic neurons in an animal model of Parkinson's disease, because these neurons express 4,10 and internalize NTSR1. 5,8,11 The efficacy of the NT-polyplex is supported by the morphological and functional recovery from dopaminergic neurodegeneration in experimental hemiparkinsonism. 12 The neuroblastoma, an embryonic tumor derived from the neural crest, is the second most common solid tumor in childhood, 13 with invasion of locoregional nodes and distant metastasis in approximately 75% of cases in children older than 1 year.…”

Section: Introductionmentioning

confidence: 99%

“…The NTpolyplex could be a specific tool to transfer therapeutic genes to neuroblastoma tumors because several human cell lines express NTSR1. 16,17 In this work, the murine neuroblastoma N1E-115 cell line, which has been efficiently transfected by NT-polyplex in culture 1,2,8 because they overexpressed the NTSR1, 18 was allografted in athymic mice to develop an animal model of a neuroblastoma tumor. We hypothesized that the NTpolyplex will be able to transfer genes into neuroblastoma tumor cells after its injection into the tumor or through the blood stream.…”

Section: Introductionmentioning

confidence: 99%

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NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

et al. 2009

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and 4 Molecular and Steroid hormones, Neurotensin and Tumor Progression INSERM UPMC Cdr Saint-Antoine Eq 7, Paris, France Neurotensin (NT)-polyplex is a nonviral system for the targeted gene delivery to cells that express and internalize the high-affinity NT receptor (NTSR1). In hemiparkinsonian rats, we previously demonstrated the morphological and functional recovery from dopaminergic neurodegeneration using the NT-polyplex as a vehicle to transfect a neurotrophic gene. The main objective of this work was to demonstrate the feasibility of NT-polyplex to transfect reporter or therapeutic genes into neuroblastoma tumors through the blood stream or by intratumoral injection. N1E-115 cells known to express NTSR1 were allografted into athymic mice to generate the neuroblastoma tumor model. Both routes of administration allowed the NT-polyplex to reach and transfect tumoral cells. A low transgene expression was also detected in intestinal tract cells only after the injection into the blood stream. The transfection of the thymidine kinase (HSVTK) suicide gene followed by ganciclovir (GCV) treatment decreased the size and weight of neuroblastoma tumors by 30-50% and increased apoptosis compared to controls. This study shows the potential of the NTpolyplex as specific gene-transfer system for NTSR1 cancer cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

et al. 2009

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Neuron‐specific delivery of nucleic acids mediated by Tet1‐modified poly(ethylenimine)

Park

Lašienė

Chou

et al. 2007

The Journal of Gene Medicine

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Background-The development of minimally invasive, non-viral gene delivery vehicles for the central nervous system (CNS) is an important technology goal in the advancement of molecular therapies for neurological diseases. One approach is to deliver materials peripherally that are recognized and retrogradely transported by motor neurons toward the CNS. Tet1 is a peptide identified by Boulis and coworkers to possess the binding characteristics of tetanus toxin, which interacts specifically with motor neurons and undergoes fast, retrograde delivery to cell soma. In this work, Tet1-poly(ethylenimine) (Tet1-PEI) was synthesized and evaluated as a neurontargeted delivery vehicle.

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