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Retinal transduction profiles by high-capacity viral vectors
Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5kb) genes. Viral vectors derived from Adenovirus (Ad), Lent...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193889/ https://www.ncbi.nlm.nih.gov/pubmed/24989814 http://dx.doi.org/10.1038/gt.2014.57 |
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author | Puppo, Agostina Cesi, Giulia Marrocco, Elena Piccolo, Pasquale Jacca, Sarah Shayakhmetov, Dmitry M. Parks, Robin J. Davidson, Beverly L. Colloca, Stefano Brunetti-Pierri, Nicola Ng, Philip Donofrio, Gaetano Auricchio, Alberto |
author_facet | Puppo, Agostina Cesi, Giulia Marrocco, Elena Piccolo, Pasquale Jacca, Sarah Shayakhmetov, Dmitry M. Parks, Robin J. Davidson, Beverly L. Colloca, Stefano Brunetti-Pierri, Nicola Ng, Philip Donofrio, Gaetano Auricchio, Alberto |
author_sort | Puppo, Agostina |
collection | PubMed |
description | Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5kb) genes. Viral vectors derived from Adenovirus (Ad), Lentivirus (LV) and Herpesvirus (HV) can package large DNA sequences but do not target efficiently retinal photoreceptors (PRs) where the majority of genes responsible for IRs are expressed. Here, we have evaluated the mouse retinal transduction profiles of vectors derived from 16 different Ad serotypes, 7 LV pseudotypes, and from a bovine HV. Most of the vectors tested transduced efficiently the retinal pigment epithelium (RPE). We found that LV-GP64 tends to transduce more PRs than the canonical LV-VSVG albeit this was restricted to a narrow region. We observed more extensive PR transduction with HdAd1, 2 and 5/F35++ than with LV, although none of them outperformed the canonical HdAd5 or matched the extension of PR transduction achieved with AAV2/8. |
format | Online Article Text |
id | pubmed-4193889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41938892015-04-01 Retinal transduction profiles by high-capacity viral vectors Puppo, Agostina Cesi, Giulia Marrocco, Elena Piccolo, Pasquale Jacca, Sarah Shayakhmetov, Dmitry M. Parks, Robin J. Davidson, Beverly L. Colloca, Stefano Brunetti-Pierri, Nicola Ng, Philip Donofrio, Gaetano Auricchio, Alberto Gene Ther Article Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, the limited cargo capacity of AAV prevents their use for therapy of those inherited retinopathies (IRs) due to mutations in large (>5kb) genes. Viral vectors derived from Adenovirus (Ad), Lentivirus (LV) and Herpesvirus (HV) can package large DNA sequences but do not target efficiently retinal photoreceptors (PRs) where the majority of genes responsible for IRs are expressed. Here, we have evaluated the mouse retinal transduction profiles of vectors derived from 16 different Ad serotypes, 7 LV pseudotypes, and from a bovine HV. Most of the vectors tested transduced efficiently the retinal pigment epithelium (RPE). We found that LV-GP64 tends to transduce more PRs than the canonical LV-VSVG albeit this was restricted to a narrow region. We observed more extensive PR transduction with HdAd1, 2 and 5/F35++ than with LV, although none of them outperformed the canonical HdAd5 or matched the extension of PR transduction achieved with AAV2/8. 2014-07-03 2014-10 /pmc/articles/PMC4193889/ /pubmed/24989814 http://dx.doi.org/10.1038/gt.2014.57 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Puppo, Agostina Cesi, Giulia Marrocco, Elena Piccolo, Pasquale Jacca, Sarah Shayakhmetov, Dmitry M. Parks, Robin J. Davidson, Beverly L. Colloca, Stefano Brunetti-Pierri, Nicola Ng, Philip Donofrio, Gaetano Auricchio, Alberto Retinal transduction profiles by high-capacity viral vectors |
title | Retinal transduction profiles by high-capacity viral vectors |
title_full | Retinal transduction profiles by high-capacity viral vectors |
title_fullStr | Retinal transduction profiles by high-capacity viral vectors |
title_full_unstemmed | Retinal transduction profiles by high-capacity viral vectors |
title_short | Retinal transduction profiles by high-capacity viral vectors |
title_sort | retinal transduction profiles by high-capacity viral vectors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193889/ https://www.ncbi.nlm.nih.gov/pubmed/24989814 http://dx.doi.org/10.1038/gt.2014.57 |
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