Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers

The field of therapeutic oligonucleotides has experienced significant growth in recent years, both in terms of approved drugs and those undergoing clinical trials. This expansion has transformed it into a rapidly evolving area of research. However, their cellular internalization remains a major limi...

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Detalles Bibliográficos
Autores: Navarro, Natalia, Serantes, Sergio, Aviñó, Anna, Fàbrega, Carme, Eritja Casadellà, Ramón
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/341836
Acceso en línea:http://hdl.handle.net/10261/341836
https://api.elsevier.com/content/abstract/scopus_id/85179702999
Access Level:acceso abierto
Palabra clave:Therapeutics
Cellular uptake
Lipid conjugates
Oleic acid
Oligonucleotides
solid-phase synthesis
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spelling Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake EnhancersNavarro, NataliaSerantes, SergioAviñó, AnnaFàbrega, CarmeEritja Casadellà, RamónTherapeuticsCellular uptakeLipid conjugatesOleic acidOligonucleotidessolid-phase synthesisThe field of therapeutic oligonucleotides has experienced significant growth in recent years, both in terms of approved drugs and those undergoing clinical trials. This expansion has transformed it into a rapidly evolving area of research. However, their cellular internalization remains a major limitation for the clinical application of oligonucleotides. To address this limitation, we report different strategies for the synthesis of specialized solid supports for the direct synthesis of 3?-oleyl-oligonucleotides by means of an L-threoninol derivative. A series of in vitro cell experiments were conducted to evaluate the potential of this strategy for enhanced cellular uptake. The results suggest that lipid conjugation enhances cellular uptake and facilitates oligonucleotide intracellular trafficking. Given these findings, the modification of therapeutic oligonucleotides through the attachment of lipidic moieties using a threoninol linker emerges as a valuable strategy to enhance their cellular internalization.This work was financially supported by the Spanish Ministerio de Ciencia e Innovación (MICINN) (Projects PID2020-118145RB-I00 and CPP2021-008792 and a predoctoral contract grant (PRE2021-097856) to N.N.), and by Agència Valenciana de la Innovació, Generalitat Valenciana (Prometeo/2020/081). This research was also supported by the Centro de Investigación Biomédica en Red en Bioingeniería, Biomaterialesmy Nanomedicina (CB06/01/0019), Instituto de Salud Carlos III, and the European Regional Development Fund (ERDF). Oligonucleotide synthesis was performed by the ICTS ‘NANBIOSIS’ and specifically by the oligonucleotide synthesis platform (OSP) U29 at the Institut de Química Avançada de Catalunya-Consejo Superior de Investigaciones Científicas (IQAC-CSIC) (https://www.nanbiosis.es/portfolio/u29-oligonucleotide- synthesis-platform-osp/). S.S. acknowledges Conexión Nanomedicina, Consejo Superior de Investigaciones Científicas (CSIC) for a JAE intro grant (JAEICU-21-IQM-29).Peer reviewedGeorg Thieme Verlag0000-0001-5383-9334Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/341836https://api.elsevier.com/content/abstract/scopus_id/85179702999reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSynlett10.1055/s-0042-1751528Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3418362026-05-22T06:33:51Z
dc.title.none.fl_str_mv Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
title Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
spellingShingle Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
Navarro, Natalia
Therapeutics
Cellular uptake
Lipid conjugates
Oleic acid
Oligonucleotides
solid-phase synthesis
title_short Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
title_full Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
title_fullStr Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
title_full_unstemmed Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
title_sort Synthesis and Evaluation of 3′-Oleyl-Oligonucleotide Conjugates as Potential Cellular Uptake Enhancers
dc.creator.none.fl_str_mv Navarro, Natalia
Serantes, Sergio
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
author Navarro, Natalia
author_facet Navarro, Natalia
Serantes, Sergio
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
author_role author
author2 Serantes, Sergio
Aviñó, Anna
Fàbrega, Carme
Eritja Casadellà, Ramón
author2_role author
author
author
author
dc.contributor.none.fl_str_mv 0000-0001-5383-9334
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Therapeutics
Cellular uptake
Lipid conjugates
Oleic acid
Oligonucleotides
solid-phase synthesis
topic Therapeutics
Cellular uptake
Lipid conjugates
Oleic acid
Oligonucleotides
solid-phase synthesis
description The field of therapeutic oligonucleotides has experienced significant growth in recent years, both in terms of approved drugs and those undergoing clinical trials. This expansion has transformed it into a rapidly evolving area of research. However, their cellular internalization remains a major limitation for the clinical application of oligonucleotides. To address this limitation, we report different strategies for the synthesis of specialized solid supports for the direct synthesis of 3?-oleyl-oligonucleotides by means of an L-threoninol derivative. A series of in vitro cell experiments were conducted to evaluate the potential of this strategy for enhanced cellular uptake. The results suggest that lipid conjugation enhances cellular uptake and facilitates oligonucleotide intracellular trafficking. Given these findings, the modification of therapeutic oligonucleotides through the attachment of lipidic moieties using a threoninol linker emerges as a valuable strategy to enhance their cellular internalization.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/341836
https://api.elsevier.com/content/abstract/scopus_id/85179702999
url http://hdl.handle.net/10261/341836
https://api.elsevier.com/content/abstract/scopus_id/85179702999
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Synlett
10.1055/s-0042-1751528
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Georg Thieme Verlag
publisher.none.fl_str_mv Georg Thieme Verlag
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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