Cargando…
In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles
Many rare diseases course with affectation of neurosensory organs. Among them, the neuroepithelial retina is very vulnerable due to constant light/oxidative stress, but it is also the most accessible and amenable to gene manipulation. Currently, gene addition therapies targeting retinal tissue (eith...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523520/ https://www.ncbi.nlm.nih.gov/pubmed/30970664 http://dx.doi.org/10.3390/genes10040289 |
_version_ | 1783419352854298624 |
---|---|
author | Trigueros, Sònia B. Domènech, Elena Toulis, Vasileios Marfany, Gemma |
author_facet | Trigueros, Sònia B. Domènech, Elena Toulis, Vasileios Marfany, Gemma |
author_sort | Trigueros, Sònia |
collection | PubMed |
description | Many rare diseases course with affectation of neurosensory organs. Among them, the neuroepithelial retina is very vulnerable due to constant light/oxidative stress, but it is also the most accessible and amenable to gene manipulation. Currently, gene addition therapies targeting retinal tissue (either photoreceptors or the retinal pigment epithelium), as a therapy for inherited retinal dystrophies, use adeno-associated virus (AAV)-based approaches. However, efficiency and safety of therapeutic strategies are relevant issues that are not always resolved in virus-based gene delivery and alternative methodologies should be explored. Based on our experience, we are currently assessing the novel physical properties at the nanoscale of inorganic gold nanoparticles for delivering genes to the retinal pigment epithelium (RPE) as a safe and efficient alternative approach. In this work, we present our preliminary results using DNA-wrapped gold nanoparticles (DNA-gold NPs) for successful in vitro gene delivery on human retinal pigment epithelium cell cultures, as a proof-of-principle to assess its feasibility for retina in vivo gene delivery. Our results show faster expression of a reporter gene in cells transfected with DNA-gold NPs compared to DNA-liposome complexes. Furthermore, we show that the DNA-gold NPs follow different uptake, internalization and intracellular vesicle trafficking routes compared to pristine NPs. |
format | Online Article Text |
id | pubmed-6523520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65235202019-06-03 In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles Trigueros, Sònia B. Domènech, Elena Toulis, Vasileios Marfany, Gemma Genes (Basel) Article Many rare diseases course with affectation of neurosensory organs. Among them, the neuroepithelial retina is very vulnerable due to constant light/oxidative stress, but it is also the most accessible and amenable to gene manipulation. Currently, gene addition therapies targeting retinal tissue (either photoreceptors or the retinal pigment epithelium), as a therapy for inherited retinal dystrophies, use adeno-associated virus (AAV)-based approaches. However, efficiency and safety of therapeutic strategies are relevant issues that are not always resolved in virus-based gene delivery and alternative methodologies should be explored. Based on our experience, we are currently assessing the novel physical properties at the nanoscale of inorganic gold nanoparticles for delivering genes to the retinal pigment epithelium (RPE) as a safe and efficient alternative approach. In this work, we present our preliminary results using DNA-wrapped gold nanoparticles (DNA-gold NPs) for successful in vitro gene delivery on human retinal pigment epithelium cell cultures, as a proof-of-principle to assess its feasibility for retina in vivo gene delivery. Our results show faster expression of a reporter gene in cells transfected with DNA-gold NPs compared to DNA-liposome complexes. Furthermore, we show that the DNA-gold NPs follow different uptake, internalization and intracellular vesicle trafficking routes compared to pristine NPs. MDPI 2019-04-09 /pmc/articles/PMC6523520/ /pubmed/30970664 http://dx.doi.org/10.3390/genes10040289 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Trigueros, Sònia B. Domènech, Elena Toulis, Vasileios Marfany, Gemma In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title | In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title_full | In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title_fullStr | In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title_full_unstemmed | In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title_short | In Vitro Gene Delivery in Retinal Pigment Epithelium Cells by Plasmid DNA-Wrapped Gold Nanoparticles |
title_sort | in vitro gene delivery in retinal pigment epithelium cells by plasmid dna-wrapped gold nanoparticles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523520/ https://www.ncbi.nlm.nih.gov/pubmed/30970664 http://dx.doi.org/10.3390/genes10040289 |
work_keys_str_mv | AT triguerossonia invitrogenedeliveryinretinalpigmentepitheliumcellsbyplasmiddnawrappedgoldnanoparticles AT bdomenechelena invitrogenedeliveryinretinalpigmentepitheliumcellsbyplasmiddnawrappedgoldnanoparticles AT toulisvasileios invitrogenedeliveryinretinalpigmentepitheliumcellsbyplasmiddnawrappedgoldnanoparticles AT marfanygemma invitrogenedeliveryinretinalpigmentepitheliumcellsbyplasmiddnawrappedgoldnanoparticles |