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Delivery of oligonucleotide‐based therapeutics: challenges and opportunities

2021-04-06Journal article Open access
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dc.contributor.authorHammond, Suzan M.
dc.contributor.authorAartsma‐Rus, Annemieke
dc.contributor.authorAlves, Sandra
dc.contributor.authorBorgos, Sven E
dc.contributor.authorBuijsen, Ronald A.M.
dc.contributor.authorCollin, Rob W.J.
dc.contributor.authorCovello, Giuseppina
dc.contributor.authorDenti, Michela A.
dc.contributor.authorDesviat, Lourdes R.
dc.contributor.authorEchevarría, Lucía
dc.contributor.authorFoged, Camilla
dc.contributor.authorGaina, Gisela
dc.contributor.authorGaranto, Alejandro
dc.contributor.authorGoyenvalle, Aurelie T.
dc.contributor.authorGuzowska, Magdalena
dc.contributor.authorHolodnuka, Irina
dc.contributor.authorJones, David R.
dc.contributor.authorKrause, Sabine
dc.contributor.authorLehto, Taavi
dc.contributor.authorMontolio, Marisol
dc.contributor.authorVan Roon‐Mom, Willeke
dc.contributor.authorArechavala‐Gomeza, Virginia
dc.date.accessioned2022-03-10T16:32:16Z
dc.date.available2022-03-10T16:32:16Z
dc.date.issued2021-04-06
dc.descriptionReview
dc.description.abstractNucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid-based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid-based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide-based therapeutics.pt_PT
dc.description.sponsorshipThis work was supported by funding from Cooperation of Science and Technology (COST) Action CA17103 (networking grant to V.A-G). V.A-G holds a Miguel Servet Fellowship from the ISCIII [grant reference CPII17/00004] that is part-funded by the European Regional Development Fund (ERDF/FEDER) and also acknowledges funding from Ikerbasque (Basque Foundation for Science). S.M.H is funded by the Medical Research Council and Muscular Dystrophy UK. A.A-R receives funding from amongst others the Duchenne Parent Project, Spieren voor Spieren, the Prinses Beatrix Spierfonds, Duchenne UK and through Horizon2020 project BIND. A.G and R.W.J.C are supported by several foundations including the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Stichting Blinden-Penning, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Oogfonds Nederland, Stichting Macula Degeneratie Fonds, and Stichting Retina Nederland Fonds (who contributed through UitZicht 2015-31 and 2018-21), together with the Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden, Stichting voor Ooglijders, and Stichting Dowilvo; as well as the Foundation Fighting Blindness USA, grant no. PPA-0517-0717-RAD. R.A.M.B is supported by Hersenstichting Nederland Grant DR-2018-00253. G.G. is supported by Ministry of Research and Innovation in Romania/National Program 31N/2016/PN 16.22.02.05. S.A is supported by Project PTDC/BBB-BMD/6301/2014 (Fundação para a Ciência e a Tecnologia—MCTES, Portugal). L.R.D. is supported by Fundación Ramón Areces Grant XVII CN and Spanish Ministry of Science and Innovation (MICINN, grant PID2019-105344RB-I00). T.L is supported by Estonian Research Council grant PSG226. S.K is supported by the Friedrich-Baur-Stiftung. C.F is funded by The Danish Council for Independent Research, Technology and Production Sciences (grant number DFF-4184-00422). W.vRM is supported by ZonMw Programme Translational Research 2 [Project number 446002002], Campaign Team Huntington and AFM Telethon [Project number 20577]. S.E.B is supported by the H2020 projects B-SMART, Grant number 721058, and REFINE, Grant number 761104. A.T.G is supported by the Institut National de la santé et la recherche médicale (INSERM) and the Association Monegasque contre les myopathies (AMM). L.E. is founded by the Association Monegasque contre les myopathies (AMM).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEMBO Mol Med. 2021 Apr 9;13(4):e13243. doi: 10.15252/emmm.202013243. Epub 2021 Apr 6. Reviewpt_PT
dc.identifier.doi10.15252/emmm.202013243pt_PT
dc.identifier.issn1757-4684
dc.identifier.urihttp://hdl.handle.net/10400.18/7983
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherEMBO Press/ Wiley Open Accesspt_PT
dc.relationBrain-Specific, Modular and Active RNA Therapeutics
dc.relationRegulatory Science Framework for Nano(bio)material-based Medical Products and Devices
dc.relation.publisherversionhttps://www.embopress.org/doi/full/10.15252/emmm.202013243pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectRNA Therapeuticspt_PT
dc.subjectDeliverypt_PT
dc.subjectOligonucleotidespt_PT
dc.subjectAntisense Oligonucleotidespt_PT
dc.subjectPreclinical Modelspt_PT
dc.subjectSafetypt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenetica Humanapt_PT
dc.titleDelivery of oligonucleotide‐based therapeutics: challenges and opportunitiespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleBrain-Specific, Modular and Active RNA Therapeutics
oaire.awardTitleRegulatory Science Framework for Nano(bio)material-based Medical Products and Devices
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/721058/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/761104/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBBB-BMD%2F6301%2F2014/PT
oaire.citation.issue4pt_PT
oaire.citation.startPagee13243pt_PT
oaire.citation.titleEMBO Molecular Medicinept_PT
oaire.citation.volume13pt_PT
oaire.fundingStreamH2020
oaire.fundingStreamH2020
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication497a6c25-9272-42d8-b4fd-603bd9b1aff7
relation.isProjectOfPublication583723c4-2be4-4747-8b32-df2d11778504
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relation.isProjectOfPublication.latestForDiscovery82ca1b56-9fd8-4a11-b89d-6bc8dd3c27f1

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