Human-derived NLS enhance the gene transfer efficiency of chitosan
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10400.1/15393 |
Resumo: | Nuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Human-derived NLS enhance the gene transfer efficiency of chitosanNuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors.FCT: PTDC/BTM/ORG/28121/2017; PD/BD/52424/2013; SFRH/BD/76873/2011;PIRG-GA-2009-249314Portland PressSapientiaBitoque, DiogoMorais, JoanaOliveira, AnaSequeira, Raquel L.Calado, SofiaFortunato, Tiago M.Simão, SóniaRosa Da Costa, AnaSilva, Gabriela A.2021-04-15T17:37:06Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/15393eng0144-846310.1042/BSR20201026info: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:RCAAP2023-07-24T10:27:49Zoai:sapientia.ualg.pt:10400.1/15393Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:06:14.067478Repositório 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 |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
title |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
spellingShingle |
Human-derived NLS enhance the gene transfer efficiency of chitosan Bitoque, Diogo |
title_short |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
title_full |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
title_fullStr |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
title_full_unstemmed |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
title_sort |
Human-derived NLS enhance the gene transfer efficiency of chitosan |
author |
Bitoque, Diogo |
author_facet |
Bitoque, Diogo Morais, Joana Oliveira, Ana Sequeira, Raquel L. Calado, Sofia Fortunato, Tiago M. Simão, Sónia Rosa Da Costa, Ana Silva, Gabriela A. |
author_role |
author |
author2 |
Morais, Joana Oliveira, Ana Sequeira, Raquel L. Calado, Sofia Fortunato, Tiago M. Simão, Sónia Rosa Da Costa, Ana Silva, Gabriela A. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Bitoque, Diogo Morais, Joana Oliveira, Ana Sequeira, Raquel L. Calado, Sofia Fortunato, Tiago M. Simão, Sónia Rosa Da Costa, Ana Silva, Gabriela A. |
description |
Nuclear import is considered as one of the major limitations for non-viral gene delivery systems and the incorporation of nuclear localization signals (NLS) that mediate nuclear intake can be used as a strategy to enhance internalization of exogenous DNA. In this work, human-derived endogenous NLS peptides based on insulin growth factor binding proteins (IGFBP), namely IGFBP-3 and IGFBP-5, were tested for their ability to improve nuclear translocation of genetic material by non-viral vectors. Several strategies were tested to determine their effect on chitosan mediated transfection efficiency: co-administration with polyplexes, co-complexation at the time of polyplex formation, and covalent ligation to chitosan. Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04-15T17:37:06Z 2021 2021-01-01T00:00:00Z |
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/10400.1/15393 |
url |
http://hdl.handle.net/10400.1/15393 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0144-8463 10.1042/BSR20201026 |
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 |
Portland Press |
publisher.none.fl_str_mv |
Portland 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 |
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 |
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1799133303548149760 |