Loading...
Co-Delivery of mRNA and pDNA Using Thermally Stabilized Coacervate-Based Core-Shell Nanosystems.
Nasr, Sarah S Lee, Sangeun Thiyagarajan, Durairaj Boese, Annette Loretz, Brigitta Lehr, Claus-Michael
Nasr, Sarah S
Lee, Sangeun
Thiyagarajan, Durairaj
Boese, Annette
Loretz, Brigitta
Lehr, Claus-Michael
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2021-11-13
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 3 MB
Other Titles
Abstract
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.
Citation
Pharmaceutics. 2021 Nov 13;13(11):1924. doi: 10.3390/pharmaceutics13111924.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1999-4923
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution 4.0 International