Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems

Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility...

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Autores principales:	Sarah S. Nasr, Sangeun Lee, Durairaj Thiyagarajan, Annette Boese, Brigitta Loretz, Claus-Michael Lehr
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	nucleic acid vaccine complex coacervation nanocarriers anisotropic nanogel physical cross-linking dual loading Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/64843125f8e34c3baf987154636b6717
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spelling	oai:doaj.org-article:64843125f8e34c3baf987154636b67172021-11-25T18:41:54ZCo-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems10.3390/pharmaceutics131119241999-4923https://doaj.org/article/64843125f8e34c3baf987154636b67172021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1924https://doaj.org/toc/1999-4923Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications.Sarah S. NasrSangeun LeeDurairaj ThiyagarajanAnnette BoeseBrigitta LoretzClaus-Michael LehrMDPI AGarticlenucleic acid vaccinecomplex coacervationnanocarriersanisotropic nanogelphysical cross-linkingdual loadingPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1924, p 1924 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleic acid vaccine complex coacervation nanocarriers anisotropic nanogel physical cross-linking dual loading Pharmacy and materia medica RS1-441
spellingShingle	nucleic acid vaccine complex coacervation nanocarriers anisotropic nanogel physical cross-linking dual loading Pharmacy and materia medica RS1-441 Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
description	Co-delivery of different species of protein-encoding polynucleotides, e.g., messenger RNA (mRNA) and plasmid DNA (pDNA), using the same nanocarrier is an interesting topic that remains scarcely researched in the field of nucleic acid delivery. The current study hence aims to explore the possibility of the simultaneous delivery of mRNA (mCherry) and pDNA (pAmCyan) using a single nanocarrier. The latter is based on gelatin type A, a biocompatible, and biodegradable biopolymer of broad pharmaceutical application. A core-shell nanostructure is designed with a thermally stabilized gelatin–pDNA coacervate in its center. Thermal stabilization enhances the core’s colloidal stability and pDNA shielding effect against nucleases as confirmed by nanoparticle tracking analysis and gel electrophoresis, respectively. The stabilized, pDNA-loaded core is coated with the cationic peptide protamine sulfate to enable additional surface-loading with mRNA. The dual-loaded core-shell system transfects murine dendritic cell line DC2.4 with both fluorescent reporter mRNA and pDNA simultaneously, showing a transfection efficiency of 61.4 ± 21.6% for mRNA and 37.6 ± 19.45% for pDNA, 48 h post-treatment, whereas established commercial, experimental, and clinical transfection reagents fail. Hence, the unique co-transfectional capacity and the negligible cytotoxicity of the reported system may hold prospects for vaccination among other downstream applications.
format	article
author	Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr
author_facet	Sarah S. Nasr Sangeun Lee Durairaj Thiyagarajan Annette Boese Brigitta Loretz Claus-Michael Lehr
author_sort	Sarah S. Nasr
title	Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
title_short	Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
title_full	Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
title_fullStr	Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
title_full_unstemmed	Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems
title_sort	co-delivery of mrna and pdna using thermally stabilized coacervate-based core-shell nanosystems
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/64843125f8e34c3baf987154636b6717
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_version_	1718410775033282560

Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems

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