Delivery of Antisense Oligonucleotides Mediated by a Hydrogel System: In Vitro and In Vivo Application in the Context of Spinal Cord Injury
Biomaterials-based hydrogels are attractive drug-eluting vehicles in the context of RNA therapeutics, such as those utilizing antisense oligonucleotide or RNA interference based drugs, as they can potentially reduce systemic toxicity and enhance in vivo efficacy by increasing in situ concentrations. Here we describe the preparation of antisense oligonucleotide-loaded fibrin hydrogels exploring their applications in the context of the nervous system utilizing an organotypic dorsal root ganglion explant in vitro system and an in vivo model of spinal cord injury.
Key wordsAntisense oligonucleotides Hydrogel Fibrin Gene silencing Central nervous system Spinal cord injury Dorsal root ganglion
This work was supported by Fundação para a Ciência e a Tecnologia (FCT, Portugal) in the framework of the Harvard-Portugal Medical School Program [HMSP-ICT/0020/2010]; Project NORTE-01-0145-FEDER-000008, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Program for Competitiveness and Internationalization (POCI), Portugal 2020; by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274); Santa Casa da Misericordia de Lisboa—Prémio Neurociências Mello e Castro (MC-1068-2015) and the fellowships SFRH/BPD/108738/2015 (FCT) to P.M.D.M and Infarmed (FIS-FIS-2015-01_CCV_20150630-88) to M.T.
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