Gene Therapy for Retinitis Pigmentosa Caused by MFRP Mutations: Human Phenotype and Preliminary Proof of Concept
| Autor: | Margarita Matias-Florentino, Sanford L. Boye, Juan Carlos Zenteno, Qiuhong Li, William W. Hauswirth, Jackie Estreicher, Andy W. Neeley, Vince A. Chiodo, Tomas S. Aleman, Astra Dinculescu, Seok-Hong Min, Xuan Liu, Xinhua Shu, Wen-Tao Deng, Alejandro J. Roman, Alexander Sumaroka, Beatriz Buentello-Volante, Sharon B. Schwartz, Artur V. Cideciyan, Samuel G. Jacobson, Wei Chieh Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Retinal degeneration
Pathology medicine.medical_specialty Gene therapy of the human retina Retinal pigment epithelium medicine.diagnostic_test Retinal Gene delivery Apical membrane Biology medicine.disease Molecular biology chemistry.chemical_compound medicine.anatomical_structure chemistry Retinitis pigmentosa Genetics medicine Molecular Medicine Molecular Biology Research Articles Electroretinography |
| Popis: | Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy. |
| Databáze: | OpenAIRE |
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