A Nanoprimer To Improve the Systemic Delivery of siRNA and mRNA
| Autor: | Matthieu Germain, Robert Langer, Audrey Darmon, Marion Paolini, Nell R M Saunders, Owen S. Fenton, Francis Mpambani, Laurence Poul, Maxime Bergère, Julie Devalliere, Oceane Jibault |
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| Rok vydání: | 2020 |
| Předmět: |
Bioengineering
02 engineering and technology Pharmacology chemistry.chemical_compound Mice Drug Delivery Systems Gene silencing Animals General Materials Science RNA Messenger RNA Small Interfering Messenger RNA Liposome Factor VII Mechanical Engineering RNA General Chemistry Mononuclear phagocyte system 021001 nanoscience & nanotechnology Condensed Matter Physics Lipids Bioavailability chemistry Nucleic acid Hepatocytes Nanoparticles 0210 nano-technology |
| Zdroj: | Nano letters. 20(6) |
| ISSN: | 1530-6992 |
| Popis: | Despite tremendous interest in gene therapies, the systemic delivery of nucleic acids still faces substantial challenges. To successfully administer nucleic acids, one approach is to encapsulate them in lipid nanoparticles (LNPs). However, LNPs administered intravenously substantially accumulate in the liver where they are taken up by the reticuloendothelial system (RES). Here, we administer prior to the LNPs a liposome designed to transiently occupy liver cells, the Nanoprimer. This study demonstrates that the pretreatment of mice with the Nanoprimer decreases the LNPs' uptake by the RES. By accumulating rapidly in the liver cells, the Nanoprimer improves the bioavailability of the LNPs encapsulating human erythropoietin (hEPO) mRNA or factor VII (FVII) siRNA, leading respectively to more hEPO production (by 32%) or FVII silencing (by 49%). The use of the Nanoprimer offers a new strategy to improve the systemic delivery of RNA-based therapeutics. |
| Databáze: | OpenAIRE |
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