Effective delivery of large genes to the retina by dual AAV vectors
| العنوان: | Effective delivery of large genes to the retina by dual AAV vectors |
|---|---|
| المؤلفون: | Andrea Sommella, Elena Marrocco, Giulia Cesi, Massimo Giunti, Gwyneth Jane Farrar, Settimio Rossi, Carolina Iodice, Roman S. Polishchuk, Sonia de Simone, Alberto Auricchio, Arpad Palfi, Ivana Trapani, Pasqualina Colella |
| المساهمون: | Trapani I, Colella P, Sommella A, Iodice C, Cesi G, De Simone S, Marrocco E, Rossi S, Giunti M, Palfi A, Jane Farrar G, Polishchuk R, Auricchio A, Trapani, I, Colella, P, Sommella, A, Iodice, C, Cesi, G, De Simone, S, Marrocco, E, Rossi, S, Giunti, M, Palfi, A, Jane Farrar, G, Polishchuk, R, Auricchio, Alberto, de Simone, S, Rossi, Settimio, Farrar, Gj, Auricchio, A. |
| المصدر: | EMBO Molecular Medicine |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | retina, Genetic enhancement, viruses, Sus scrofa, Retinal Pigment Epithelium, ABCA4, Trans-Splicing, retinal gene therapy, Transduction (genetics), Macular Degeneration, Mice, 0302 clinical medicine, Transduction, Genetic, Stargardt Disease, Genetics, 0303 health sciences, Melanosomes, Gene Transfer Techniques, AAV, Dependovirus, gene therapy, MYO7A, Phenotype, Myosin VIIa, RNA splicing, Molecular Medicine, Usher Syndromes, Photoreceptor Cells, Vertebrate, Research Article, Rhodopsin, Genetic Vectors, Computational biology, Biology, Myosins, Injections, Lipofuscin, 03 medical and health sciences, medicine, Animals, Humans, Gene, 030304 developmental biology, HEK 293 cells, medicine.disease, Stargardt disease, Mice, Inbred C57BL, Disease Models, Animal, HEK293 Cells, ATP-Binding Cassette Transporters, Homologous recombination, 030217 neurology & neurosurgery |
| الوصف: | Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, AAV’s limited cargo capacity prevents its application to therapies of inherited retinal diseases due to mutations of genes over 5 kb, like Stargardt’s disease (STGD) and Usher syndrome type IB (USH1B). Previous methods based on ‘forced’ packaging of large genes into AAV capsids may not be easily translated to the clinic due to the generation of genomes of heterogeneous size which raise safety concerns. Taking advantage of AAV’s ability to concatemerize, we generated dual AAV vectors which reconstitute a large gene by either splicing (trans-splicing), homologous recombination (overlapping), or a combination of the two (hybrid). We found that dual trans-splicing and hybrid vectors transduce efficiently mouse and pig photoreceptors to levels that, albeit lower than those achieved with a single AAV, resulted in significant improvement of the retinal phenotype of mouse models of STGD and USH1B. Thus, dual AAV trans-splicing or hybrid vectors are an attractive strategy for gene therapy of retinal diseases that require delivery of large genes. |
| وصف الملف: | ELETTRONICO |
| تدمد: | 1757-4684 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c51efd9d586ae45bea7e76a75af45caTest https://pubmed.ncbi.nlm.nih.gov/24150896Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c51efd9d586ae45bea7e76a75af45ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574684 |
|---|