RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition
Autor: | Mathias Viard, Lauren Rackley, Lauren Lee, Ridhima Juneja, Marina A. Dobrovolskaia, Elisa Franco, Jacqueline Salotti, Jaclyn Smollett, Kirill A. Afonin, Mubin Tarannum, Peter F. Johnson, J.U.A. Vivero-Escoto, Kyle Roark, Jaimie Marie Stewart, Justin R. Halman, Ankit Shah, Andrey Krokhotin, Nikolay V. Dokholyan |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
chemistry.chemical_classification Small interfering RNA Materials science In silico RNA Biomaterial 02 engineering and technology 021001 nanoscience & nanotechnology Condensed Matter Physics Non-coding RNA Article Electronic Optical and Magnetic Materials Cell biology Biomaterials 03 medical and health sciences 030104 developmental biology chemistry RNA interference Electrochemistry Gene silencing Nucleotide 0210 nano-technology |
Zdroj: | Advanced functional materials. 28(48) |
ISSN: | 1616-301X |
Popis: | RNA is a versatile biomaterial that can be used to engineer nanoassemblies for personalized treatment of various diseases. Despite promising advancements, the design of RNA nanoassemblies with minimal recognition by the immune system remains a major challenge. Here, an approach is reported to engineer RNA fibrous structures to operate as a customizable platform for efficient coordination of siRNAs and for maintaining low immunostimulation. Functional RNA fibers are studied in silico and their formation is confirmed by various experimental techniques and visualized by atomic force microscopy (AFM). It is demonstrated that the RNA fibers offer multiple advantages among which are: i) programmability and modular design that allow for simultaneous controlled delivery of multiple siRNAs and fluorophores, ii) reduced immunostimulation when compared to other programmable RNA nanoassemblies, and iii) simple production protocol for endotoxin-free fibers with the option of their cotranscriptional assembly. Furthermore, it is shown that functional RNA fibers can be efficiently delivered with various organic and inorganic carriers while retaining their structural integrity in cells. Specific gene silencing triggered by RNA fibers is assessed in human breast cancer and melanoma cell lines, with the confirmed ability of functional fibers to selectively target single nucleotide mutations. |
Databáze: | OpenAIRE |
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