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.