Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection
Autor(a) principal: | |
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Data de Publicação: | 2007 |
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/1822/67717 |
Resumo: | In utero gene transfer to the developing lung may have clinical or research applications. In this study, we developed a new method for specifically targeting the fetal rat lung with adeno and lentiviral vectors encoding the enhanced green fluorescence protein (EGFP) marker gene at E15.5 using ultrasound biomicroscopy (UBM). Survival rate, morphometric parameters, viral biodistribution, and lung transduction efficiency were analyzed and compared to the intra-amniotic route of administration. Expression of EGFP started as early as 24 and 72 h after the injection of adenoviral and lentiviral vectors, respectively. Both vectors transduced lung parenchyma with gene expression limited to interstitial cells of the injected region, in contrast to intra-amniotic injection, which targeted the pulmonary epithelium. Expression of EGFP was most intense at E18.5 and E21.5 for adenoviral and lentiviral vectors, respectively. In contrast to lentivirus, adenoviral expression significantly declined until final analysis at 1 week of age. This study demonstrates the feasibility of targeting the fetal rat lung interstitium with viral vectors under UBM guidance during the pseudoglandular stage. This model system may facilitate in vivo studies of dynamic lung morphogenesis and could provide insight into the efficacy of prenatal gene transfer strategies for treatment of specific lung disorders. |
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Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injectionAdenoviridaeAnimalsFemaleGene ExpressionGenetic VectorsGreen Fluorescent ProteinsImmunohistochemistryInjectionsLentivirusLungMicroscopy, AcousticMicroscopy, FluorescencePregnancyRatsRats, Sprague-DawleyRecombinant Fusion ProteinsGene Transfer TechniquesCiências Médicas::Medicina BásicaScience & TechnologyIn utero gene transfer to the developing lung may have clinical or research applications. In this study, we developed a new method for specifically targeting the fetal rat lung with adeno and lentiviral vectors encoding the enhanced green fluorescence protein (EGFP) marker gene at E15.5 using ultrasound biomicroscopy (UBM). Survival rate, morphometric parameters, viral biodistribution, and lung transduction efficiency were analyzed and compared to the intra-amniotic route of administration. Expression of EGFP started as early as 24 and 72 h after the injection of adenoviral and lentiviral vectors, respectively. Both vectors transduced lung parenchyma with gene expression limited to interstitial cells of the injected region, in contrast to intra-amniotic injection, which targeted the pulmonary epithelium. Expression of EGFP was most intense at E18.5 and E21.5 for adenoviral and lentiviral vectors, respectively. In contrast to lentivirus, adenoviral expression significantly declined until final analysis at 1 week of age. This study demonstrates the feasibility of targeting the fetal rat lung interstitium with viral vectors under UBM guidance during the pseudoglandular stage. This model system may facilitate in vivo studies of dynamic lung morphogenesis and could provide insight into the efficacy of prenatal gene transfer strategies for treatment of specific lung disorders.FCT Grant (SFRH/BD/15260/2004) on behalf of the FCT Grant POCI/SAU-OBS/56428/2004Cell PressUniversidade do MinhoHenriques-Coelho, TiagoGonzaga, SílviaEndo, MasayukiZoltick, Philip W.Davey, MarcusLeite-Moreira, Adelino F.Correia-Pinto, JorgeFlake, Alan W.2007-022007-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67717engHenriques-Coelho, T., Gonzaga, S., Endo, M., Zoltick, P. W., Davey, M., et. al.(2007). Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection. Molecular Therapy, 15(2), 340-3471525-00161525-002410.1038/sj.mt.630005717235312https://www.sciencedirect.com/science/article/pii/S1525001616312874info: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:RCAAP2023-07-21T12:22:07Zoai:repositorium.sdum.uminho.pt:1822/67717Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:15:33.877101Repositório 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 |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
title |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
spellingShingle |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection Henriques-Coelho, Tiago Adenoviridae Animals Female Gene Expression Genetic Vectors Green Fluorescent Proteins Immunohistochemistry Injections Lentivirus Lung Microscopy, Acoustic Microscopy, Fluorescence Pregnancy Rats Rats, Sprague-Dawley Recombinant Fusion Proteins Gene Transfer Techniques Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
title_full |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
title_fullStr |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
title_full_unstemmed |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
title_sort |
Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection |
author |
Henriques-Coelho, Tiago |
author_facet |
Henriques-Coelho, Tiago Gonzaga, Sílvia Endo, Masayuki Zoltick, Philip W. Davey, Marcus Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
author_role |
author |
author2 |
Gonzaga, Sílvia Endo, Masayuki Zoltick, Philip W. Davey, Marcus Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Henriques-Coelho, Tiago Gonzaga, Sílvia Endo, Masayuki Zoltick, Philip W. Davey, Marcus Leite-Moreira, Adelino F. Correia-Pinto, Jorge Flake, Alan W. |
dc.subject.por.fl_str_mv |
Adenoviridae Animals Female Gene Expression Genetic Vectors Green Fluorescent Proteins Immunohistochemistry Injections Lentivirus Lung Microscopy, Acoustic Microscopy, Fluorescence Pregnancy Rats Rats, Sprague-Dawley Recombinant Fusion Proteins Gene Transfer Techniques Ciências Médicas::Medicina Básica Science & Technology |
topic |
Adenoviridae Animals Female Gene Expression Genetic Vectors Green Fluorescent Proteins Immunohistochemistry Injections Lentivirus Lung Microscopy, Acoustic Microscopy, Fluorescence Pregnancy Rats Rats, Sprague-Dawley Recombinant Fusion Proteins Gene Transfer Techniques Ciências Médicas::Medicina Básica Science & Technology |
description |
In utero gene transfer to the developing lung may have clinical or research applications. In this study, we developed a new method for specifically targeting the fetal rat lung with adeno and lentiviral vectors encoding the enhanced green fluorescence protein (EGFP) marker gene at E15.5 using ultrasound biomicroscopy (UBM). Survival rate, morphometric parameters, viral biodistribution, and lung transduction efficiency were analyzed and compared to the intra-amniotic route of administration. Expression of EGFP started as early as 24 and 72 h after the injection of adenoviral and lentiviral vectors, respectively. Both vectors transduced lung parenchyma with gene expression limited to interstitial cells of the injected region, in contrast to intra-amniotic injection, which targeted the pulmonary epithelium. Expression of EGFP was most intense at E18.5 and E21.5 for adenoviral and lentiviral vectors, respectively. In contrast to lentivirus, adenoviral expression significantly declined until final analysis at 1 week of age. This study demonstrates the feasibility of targeting the fetal rat lung interstitium with viral vectors under UBM guidance during the pseudoglandular stage. This model system may facilitate in vivo studies of dynamic lung morphogenesis and could provide insight into the efficacy of prenatal gene transfer strategies for treatment of specific lung disorders. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-02 2007-02-01T00:00:00Z |
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/1822/67717 |
url |
http://hdl.handle.net/1822/67717 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Henriques-Coelho, T., Gonzaga, S., Endo, M., Zoltick, P. W., Davey, M., et. al.(2007). Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection. Molecular Therapy, 15(2), 340-347 1525-0016 1525-0024 10.1038/sj.mt.6300057 17235312 https://www.sciencedirect.com/science/article/pii/S1525001616312874 |
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 |
Cell Press |
publisher.none.fl_str_mv |
Cell Press |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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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 |
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