Cationic polyene phospholipids as DNA carriers for ocular gene therapy
Autor(a) principal: | |
---|---|
Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/9874 |
Resumo: | Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy. |
id |
RCAP_b55f167811aba42e2bc255e3b1c87224 |
---|---|
oai_identifier_str |
oai:sapientia.ualg.pt:10400.1/9874 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Cationic polyene phospholipids as DNA carriers for ocular gene therapyCationsCell lineCholesterolDNAEpithelium, cornealEyeGene transfer techniquesGenetic therapyGenetic vectorsHumansLiposomesPhosphatidylethanolaminesPhospholipidsPlasmidsPolyenesRetinal pigmentsTransfectionRecent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy.Hindawi Publishing CorporationSapientiaMachado, SusanaCalado, SofiaBitoque, DiogoOliveira, Ana VanessaØpstad, Christer L.Zeeshan, MuhammadSliwka, Hans-RichardPartali, VassiliaPungente, Michael D.Silva, Gabriela2017-07-19T14:33:55Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/9874engAUT: GAS02236;10.1155/2014/703253info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:21:25Zoai:sapientia.ualg.pt:10400.1/9874Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:01:42.097464Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
title |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
spellingShingle |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy Machado, Susana Cations Cell line Cholesterol DNA Epithelium, corneal Eye Gene transfer techniques Genetic therapy Genetic vectors Humans Liposomes Phosphatidylethanolamines Phospholipids Plasmids Polyenes Retinal pigments Transfection |
title_short |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
title_full |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
title_fullStr |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
title_full_unstemmed |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
title_sort |
Cationic polyene phospholipids as DNA carriers for ocular gene therapy |
author |
Machado, Susana |
author_facet |
Machado, Susana Calado, Sofia Bitoque, Diogo Oliveira, Ana Vanessa Øpstad, Christer L. Zeeshan, Muhammad Sliwka, Hans-Richard Partali, Vassilia Pungente, Michael D. Silva, Gabriela |
author_role |
author |
author2 |
Calado, Sofia Bitoque, Diogo Oliveira, Ana Vanessa Øpstad, Christer L. Zeeshan, Muhammad Sliwka, Hans-Richard Partali, Vassilia Pungente, Michael D. Silva, Gabriela |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Machado, Susana Calado, Sofia Bitoque, Diogo Oliveira, Ana Vanessa Øpstad, Christer L. Zeeshan, Muhammad Sliwka, Hans-Richard Partali, Vassilia Pungente, Michael D. Silva, Gabriela |
dc.subject.por.fl_str_mv |
Cations Cell line Cholesterol DNA Epithelium, corneal Eye Gene transfer techniques Genetic therapy Genetic vectors Humans Liposomes Phosphatidylethanolamines Phospholipids Plasmids Polyenes Retinal pigments Transfection |
topic |
Cations Cell line Cholesterol DNA Epithelium, corneal Eye Gene transfer techniques Genetic therapy Genetic vectors Humans Liposomes Phosphatidylethanolamines Phospholipids Plasmids Polyenes Retinal pigments Transfection |
description |
Recent success in the treatment of congenital blindness demonstrates the potential of ocular gene therapy as a therapeutic approach. The eye is a good target due to its small size, minimal diffusion of therapeutic agent to the systemic circulation, and low immune and inflammatory responses. Currently, most approaches are based on viral vectors, but efforts continue towards the synthesis and evaluation of new nonviral carriers to improve nucleic acid delivery. Our objective is to evaluate the efficiency of novel cationic retinoic and carotenoic glycol phospholipids, designated C20-18, C20-20, and C30-20, to deliver DNA to human retinal pigmented epithelium (RPE) cells. Liposomes were produced by solvent evaporation of ethanolic mixtures of the polyene compounds and coformulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol (Chol). Addition of DNA to the liposomes formed lipoplexes, which were characterized for binding, size, biocompatibility, and transgene efficiency. Lipoplex formulations of suitable size and biocompatibility were assayed for DNA delivery, both qualitatively and quantitatively, using RPE cells and a GFP-encoding plasmid. The retinoic lipoplex formulation with DOPE revealed a transfection efficiency comparable to the known lipid references 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (EPC) and GeneJuice. The results demonstrate that cationic polyene phospholipids have potential as DNA carriers for ocular gene therapy. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2014-01-01T00:00:00Z 2017-07-19T14:33:55Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/9874 |
url |
http://hdl.handle.net/10400.1/9874 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
AUT: GAS02236; 10.1155/2014/703253 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hindawi Publishing Corporation |
publisher.none.fl_str_mv |
Hindawi Publishing Corporation |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799133247286804480 |