Study of Oligonucleotides Access and Distribution in Human Peripheral Blood Mononuclear Cells

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorHospital General Universitario de Castellón-
Autor(es): dc.contributorInstituto de Investigación Sanitaria La Fe-
Autor(es): dc.contributorUniversity of Valencia-
Autor(es): dc.contributorMaimonides Biomedical Research Institute of Cordoba (IMIBIC)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorFernández Delgado, Manuel-
Autor(es): dc.creatorSendra, Luis-
Autor(es): dc.creatorHerrero, María José-
Autor(es): dc.creatorOlivera-Pasquini, Gladys G.-
Autor(es): dc.creatorDuharte, Alexander Batista-
Autor(es): dc.creatorAliño, Salvador F.-
Data de aceite: dc.date.accessioned2025-08-21T19:55:06Z-
Data de disponibilização: dc.date.available2025-08-21T19:55:06Z-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2023-03-01-
Data de envio: dc.date.issued2022-05-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/ijms23105839-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241020-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241020-
Descrição: dc.descriptionTherapeutic oligonucleotides have achieved great clinical interest since their approval as drug agents by regulatory agencies but their access and distribution in blood cells are not completely known. We evaluated by flow cytometry the ability of short fluorescent scramble oligonucleotides (ON*) to access human peripheral blood mononuclear cells (PBMC) after incubating with ON* during 1 h and 7 days of culture follow-up ‘in vitro’. Blood samples were treated with chemically modified oligonucleotides (phosphorothioate backbone and 2′ O-Me ends) to resist nuclease digestion under culture conditions. The ON* internalization was determined after discarding the membrane-associated fluorescence by trypan blue quenching. Whereas the oligonucleotide accessed neutro-phils and monocytes rapidly, achieving their maximum in 1 h and 24 h, respectively, lymphocytes required 7 days to achieve the maximum (80% of cells) transfection. The ON*ability to access lym-phocyte types (T, B, and NK) and T cell subtypes (CD4+, CD8+, and CD4-CD8-) were similar, with T cells being more accessible. Regulatory CD4+ and CD8+ T cells were classified in low and high Foxp3 expressers, whose expression proved not to alter the ON* internalization during the first hour, achieving 53% of CD4+Foxp3+ and 40% of CD8+Foxp3+ cells. Our results contribute to understanding and improving the management of therapeutic ONs.-
Descrição: dc.descriptionService of Hematology and Hemotherapy Hospital General Universitario de Castellón-
Descrição: dc.descriptionFarmacogenetics and Gene Therapy Group Instituto de Investigación Sanitaria La Fe, Av. Fernando Abril Martorell, 106-
Descrição: dc.descriptionGene Therapy and Pharmacogenomics Group Department of Pharmacology Faculty of Medicine University of Valencia, Av. Blasco Ibáñez 15-
Descrição: dc.descriptionGC01 Immunology and Allergy Group Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menéndez Pidal, s/n-
Descrição: dc.descriptionLaboratório de Imunología Clínica Dpto Analises Clinicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP), Rod. Araraquara-Jaú—Km 1, Campus Ville, SP-
Descrição: dc.descriptionLaboratório de Imunología Clínica Dpto Analises Clinicas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista (UNESP), Rod. Araraquara-Jaú—Km 1, Campus Ville, SP-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Molecular Sciences-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCD8+ Treg-
Palavras-chave: dc.subjectcell uptake-
Palavras-chave: dc.subjectflow cytometry-
Palavras-chave: dc.subjectfluorescent labeling-
Palavras-chave: dc.subjectFOXP3-
Palavras-chave: dc.subjectoligonucleotides-
Palavras-chave: dc.subjectPBMC-
Palavras-chave: dc.subjectquenching-
Palavras-chave: dc.subjectTreg-
Título: dc.titleStudy of Oligonucleotides Access and Distribution in Human Peripheral Blood Mononuclear Cells-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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