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RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition
Author(s) -
Rackley Lauren,
Stewart Jaimie Marie,
Salotti Jacqueline,
Krokhotin Andrey,
Shah Ankit,
Halman Justin R.,
Juneja Ridhima,
Smollett Jaclyn,
Lee Lauren,
Roark Kyle,
Viard Mathias,
Tarannum Mubin,
ViveroEscoto Juan,
Johnson Peter F.,
Dobrovolskaia Marina A.,
Dokholyan Nikolay V.,
Franco Elisa,
Afonin Kirill A.
Publication year - 2018
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201805959
Subject(s) - rna , small interfering rna , materials science , nanotechnology , trans acting sirna , rna interference , rna silencing , microbiology and biotechnology , computational biology , biology , gene , genetics
Abstract 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.