000285737 001__ 285737
000285737 005__ 20260320150917.0
000285737 0247_ $$2doi$$a10.1016/j.jddst.2026.108171
000285737 0247_ $$2ISSN$$a1157-1489
000285737 0247_ $$2ISSN$$a1773-2247
000285737 037__ $$aDZNE-2026-00294
000285737 082__ $$a610
000285737 1001_ $$0P:(DE-2719)9001934$$aMartinez Dominguez, Maria Victoria$$b0$$eFirst author$$udzne
000285737 245__ $$aManufacturing and testing of a polymer formulation for long-time release delivery of antisense oligonucleotides in hiPSC-derived motoneurons
000285737 260__ $$aParis$$bEd. de Santé$$c2026
000285737 3367_ $$2DRIVER$$aarticle
000285737 3367_ $$2DataCite$$aOutput Types/Journal article
000285737 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1774015608_12445
000285737 3367_ $$2BibTeX$$aARTICLE
000285737 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000285737 3367_ $$00$$2EndNote$$aJournal Article
000285737 520__ $$aAntisense oligonucleotides (ASOs) are an emerging therapeutic approach for genetically induced neurological disorders such as spinal muscular atrophy (SMA). For SMA, the Food and Drug administration (FDA)-approved ASO Nusinersen (Spinraza®) restores exon 7 inclusion in survival motor neuron (SMN) 2, leading to improved motoneuron survival. However, current administration to patients requires repeated intrathecal (IT) injections via lumbar puncture, an invasive procedure with considerable side effects. There is therefore an urgent need for more efficient and sustained drug-delivery strategies capable of overcoming these limitations. In this study, we developed and tested a system for the controlled, long-term release of Nusinersen ASO. Using motoneurons derived from human induced pluripotent stem cells (hiPSCs) from SMA and control patients, two formulations were evaluated: (I) pure ethylene vinyl acetate (EVA, 40% vinyl acetate) and (II) a composite of EVA (40% vinyl acetate) and silica (50:50 w/w). Both formulations were found to be biocompatible in the co-cultures in vitro. Moreover, the efficient uptake of ASOs and the optimization of ASO dose and time-response in motoneurons was achieved. Additionally, fluorescently labeled ASOs confirmed sustained release from the implants. Importantly, sustained polymer-released ASO significantly increased exon 7 inclusion in SMN2 transcripts and motoneuron viability over time, demonstrating therapeutic efficacy and preserved biological activity. These findings demonstrate the initial feasibility for a minimally invasive, long-term ASO delivery system that could overcome the limitation for repeated lumbar punctures in SMA patients and potentially be adapted as ASO delivery systems for other neurodegenerative diseases. 
000285737 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000285737 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de
000285737 7001_ $$aFalke, Lisa$$b1
000285737 7001_ $$0P:(DE-2719)9001978$$aBeretta, Stefania$$b2$$udzne
000285737 7001_ $$00000-0002-2661-1083$$aDauer, Katharina$$b3
000285737 7001_ $$aWagner, Karl G.$$b4
000285737 7001_ $$0P:(DE-2719)2812855$$aBoeckers, Tobias M.$$b5$$eLast author
000285737 773__ $$0PERI:(DE-600)2542935-8$$a10.1016/j.jddst.2026.108171$$gVol. 119, p. 108171 -$$p108171$$tJournal of drug delivery science and technology$$v119$$x1773-2247$$y2026
000285737 8564_ $$uhttps://pub.dzne.de/record/285737/files/DZNE-2026-00294.pdf$$yRestricted
000285737 8564_ $$uhttps://pub.dzne.de/record/285737/files/DZNE-2026-00294.pdf?subformat=pdfa$$xpdfa$$yRestricted
000285737 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001934$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000285737 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001978$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000285737 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812855$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b5$$kDZNE
000285737 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000285737 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ DRUG DELIV SCI TEC : 2022$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-27
000285737 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bJ DRUG DELIV SCI TEC : 2022$$d2024-12-27
000285737 9201_ $$0I:(DE-2719)1910002$$kAG Böckers$$lTranslational Protein Biochemistry$$x0
000285737 980__ $$ajournal
000285737 980__ $$aEDITORS
000285737 980__ $$aVDBINPRINT
000285737 980__ $$aI:(DE-2719)1910002
000285737 980__ $$aUNRESTRICTED