0000000000079646

AUTHOR

Jean Bennett

showing 3 related works from this author

Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity

2012

International audience; The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their degeneration, arises due to the loss of trophic support from RdCVF2. In contrary, the progressive loss of rod visual function of the Nxnl2-/- mouse results from a decrease in outer segment length, mediated by a cell autonomous mechanism involving the putative thioredoxin protein RdCVF2L, the second spliced product of the Nxnl2 gene. This novel signaling mechanism extends to o…

Sensory Receptor Cellsgenetic structuresCell SurvivalRNA SplicingSensory system[SDV.GEN] Life Sciences [q-bio]/GeneticsOlfactionBiologyArticleMice03 medical and health sciencesThioredoxins0302 clinical medicineRetinal Rod Photoreceptor CellsGeneticsAnimalsEye ProteinsMolecular BiologyGeneCells CulturedGenetics (clinical)030304 developmental biology[SDV.GEN]Life Sciences [q-bio]/Genetics0303 health sciencesGeneral MedicineAnatomySensory Receptor CellsCell biologyRNA splicingThioredoxinRetinal Rod Photoreceptor Cells030217 neurology & neurosurgeryFunction (biology)Human Molecular Genetics
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Suppression and Replacement Gene Therapy for Autosomal Dominant Disease in a Murine Model of Dominant Retinitis Pigmentosa

2011

For dominantly inherited disorders development of gene therapies, targeting the primary genetic lesion has been impeded by mutational heterogeneity. An example is rhodopsin-linked autosomal dominant retinitis pigmentosa with over 150 mutations in the rhodopsin gene. Validation of a mutation-independent suppression and replacement gene therapy for this disorder has been undertaken. The therapy provides a means of correcting the genetic defect in a mutation-independent manner thereby circumventing the mutational diversity. Separate adeno-associated virus (AAV) vectors were used to deliver an RNA interference (RNAi)-based rhodopsin suppressor and a codon-modified rhodopsin replacement gene res…

genetic structuresGenetic enhancementMice TransgenicPolymerase Chain ReactionPhotoreceptor cellMiceRNA interferenceRetinitis pigmentosaDrug DiscoverymedicineGeneticsElectroretinographyAnimalsGeneMolecular BiologyPharmacologyGene therapy of the human retinabiologyAutosomal dominant traitGenetic Therapymedicine.diseaseMolecular biologyDisease Models Animalmedicine.anatomical_structureRhodopsinbiology.proteinMolecular MedicineOriginal Articlesense organsRetinitis PigmentosaMolecular Therapy
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Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho–/– mouse

2015

As gene therapies for various forms of retinal degeneration progress toward human clinical trial, it will be essential to have a repertoire of safe and efficient vectors for gene delivery to the target cells. Recombinant adeno-associated virus (AAV) serotype 2/2 has been shown to be well tolerated in the human retina and has provided efficacy in human patients for some inherited retinal degenerations. In this study, the AAV2/8 and AAV2/rh10 serotypes have been compared as a means of gene delivery to mammalian photoreceptor cells using a photoreceptor specific promoter for transgene expression. Both AAV2/8 and AAV2/rh10 provided rescue of the retinal degeneration present in the rhodopsin kno…

Retinal degenerationlcsh:QH426-470TransgeneGenetic enhancementvirusesGene deliveryBiologyBioinformaticsArticlechemistry.chemical_compoundGeneticsmedicinelcsh:QH573-671Molecular BiologyRetinalcsh:CytologyRetinalmedicine.diseaseCell biologylcsh:Geneticsmedicine.anatomical_structurechemistryRhodopsinKnockout mousebiology.proteinMolecular MedicineCorrigendumMolecular Therapy. Methods & Clinical Development
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