A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles.
Previously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles cont...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005290&type=printable |
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| author | Xue Cai Zack Nash Shannon M Conley Steven J Fliesler Mark J Cooper Muna I Naash |
| author_facet | Xue Cai Zack Nash Shannon M Conley Steven J Fliesler Mark J Cooper Muna I Naash |
| author_sort | Xue Cai |
| collection | DOAJ |
| description | Previously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the wild-type retinal degeneration slow (Rds) gene were injected into the subretinal space of rds(+/-) mice on postnatal day 5. Gene expression was sustained for up to four months at levels up to four times higher than in controls injected with saline or naked DNA. The nanoparticles were taken up into virtually all photoreceptors and mediated significant structural and biochemical rescue of the disease without histological or functional evidence of toxicity. Electroretinogram recordings showed that nanoparticle-mediated gene transfer restored cone function to a near-normal level in contrast to transfer of naked plasmid DNA. Rod function was also improved. These findings demonstrate that compacted DNA nanoparticles represent a viable option for development of gene-based interventions for ocular diseases and obviate major barriers commonly encountered with non-viral based therapies. |
| format | Article |
| id | doaj-art-ca011eb9110643069edecc239df41407 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-ca011eb9110643069edecc239df414072025-08-20T02:38:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0144e529010.1371/journal.pone.0005290A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles.Xue CaiZack NashShannon M ConleySteven J FlieslerMark J CooperMuna I NaashPreviously we have shown that compacted DNA nanoparticles can drive high levels of transgene expression after subretinal injection in the mouse eye. Here we delivered compacted DNA nanoparticles containing a therapeutic gene to the retinas of a mouse model of retinitis pigmentosa. Nanoparticles containing the wild-type retinal degeneration slow (Rds) gene were injected into the subretinal space of rds(+/-) mice on postnatal day 5. Gene expression was sustained for up to four months at levels up to four times higher than in controls injected with saline or naked DNA. The nanoparticles were taken up into virtually all photoreceptors and mediated significant structural and biochemical rescue of the disease without histological or functional evidence of toxicity. Electroretinogram recordings showed that nanoparticle-mediated gene transfer restored cone function to a near-normal level in contrast to transfer of naked plasmid DNA. Rod function was also improved. These findings demonstrate that compacted DNA nanoparticles represent a viable option for development of gene-based interventions for ocular diseases and obviate major barriers commonly encountered with non-viral based therapies.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005290&type=printable |
| spellingShingle | Xue Cai Zack Nash Shannon M Conley Steven J Fliesler Mark J Cooper Muna I Naash A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. PLoS ONE |
| title | A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. |
| title_full | A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. |
| title_fullStr | A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. |
| title_full_unstemmed | A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. |
| title_short | A partial structural and functional rescue of a retinitis pigmentosa model with compacted DNA nanoparticles. |
| title_sort | partial structural and functional rescue of a retinitis pigmentosa model with compacted dna nanoparticles |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005290&type=printable |
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