dc.creator | Miliotou A.N., Pappas I.S., Spyroulias G., Vlachaki E., Tsiftsoglou A.S., Vizirianakis I.S., Papadopoulou L.C. | en |
dc.date.accessioned | 2023-01-31T09:00:10Z | |
dc.date.available | 2023-01-31T09:00:10Z | |
dc.date.issued | 2021 | |
dc.identifier | 10.1016/j.omtn.2021.09.008 | |
dc.identifier.issn | 21622531 | |
dc.identifier.uri | http://hdl.handle.net/11615/76643 | |
dc.description.abstract | The potential clinical applications of the powerful in vitro-transcribed (IVT)-mRNAs, to restore defective protein functions, strongly depend on their successful intracellular delivery and transient translation through the development of safe and efficient delivery platforms. In this study, an innovative (international patent-pending) methodology was developed, combining the IVT-mRNAs with the protein transduction domain (PTD) technology, as an efficient delivery platform. Based on the PTD technology, which enables the intracellular delivery of various cargoes intracellularly, successful conjugation of a PTD to the IVT-mRNAs was achieved and evaluated by band-shift assay and NMR spectroscopy. In addition, the PTD-IVT-mRNAs were applied and evaluated in two protein-disease models, including the mitochondrial disorder fatal infantile cardioencephalomyopathy and cytochrome c oxidase (COX) deficiency (attributed to SCO2 gene mutations) and β-thalassemia. The PTD-IVT-mRNA of SCO2 was successfully transduced and translated to the corresponding Sco2 protein inside the primary fibroblasts of a SCO2/COX-deficient patient, whereas the PTD-IVT-mRNA of β-globin was transduced and translated in bone marrow cells, derived from three β-thalassemic patients. The transducibility and the structural stability of the PDT-IVT-mRNAs, in both cases, were confirmed at the RNA and protein levels. We propose that our novel delivery platform could be clinically applicable as a protein therapy for metabolic/genetic disorders. © 2021 The Authors | en |
dc.language.iso | en | en |
dc.source | Molecular Therapy - Nucleic Acids | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116577244&doi=10.1016%2fj.omtn.2021.09.008&partnerID=40&md5=95387952029a15c596253a259d89fbbb | |
dc.subject | cytochrome c oxidase | en |
dc.subject | hemoglobin beta chain | en |
dc.subject | messenger RNA | en |
dc.subject | oxidoreductase | en |
dc.subject | 3' untranslated region | en |
dc.subject | 5' untranslated region | en |
dc.subject | animal experiment | en |
dc.subject | Article | en |
dc.subject | beta thalassemia | en |
dc.subject | bone marrow cell | en |
dc.subject | cardiomyopathy | en |
dc.subject | cloning | en |
dc.subject | comparative study | en |
dc.subject | conjugation | en |
dc.subject | controlled study | en |
dc.subject | cytochrome c oxidase deficiency | en |
dc.subject | disorders of mitochondrial functions | en |
dc.subject | encephalomyopathy | en |
dc.subject | gene mutation | en |
dc.subject | histochemistry | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | in vitro gene transfer | en |
dc.subject | in vitro study | en |
dc.subject | infant | en |
dc.subject | K-562 cell line | en |
dc.subject | mouse | en |
dc.subject | mRNA expression level | en |
dc.subject | nonhuman | en |
dc.subject | nonviral gene delivery system | en |
dc.subject | nuclear magnetic resonance spectroscopy | en |
dc.subject | promoter region | en |
dc.subject | protein domain | en |
dc.subject | protein expression level | en |
dc.subject | protein transduction domain | en |
dc.subject | Cell Press | en |
dc.title | Development of a novel PTD-mediated IVT-mRNA delivery platform for potential protein replacement therapy of metabolic/genetic disorders | en |
dc.type | journalArticle | en |