RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition.

Autor: Rackley L; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Stewart JM; Department of Bioengineering, University of California, Riverside, CA 92521, USA., Salotti J; Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Krokhotin A; Department of Biochemistry and Biophysics, University of North Carolina Chapel Hill, NC 27514, USA., Shah A; Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Sponsored by the National Cancer Institute, Frederick, MD 21702, USA., Halman JR; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Juneja R; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Smollett J; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Lee L; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Roark K; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Viard M; Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Tarannum M; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Vivero-Escoto J; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA., Johnson PF; Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Dobrovolskaia MA; Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Sponsored by the National Cancer Institute, Frederick, MD 21702, USA., Dokholyan NV; Department of Biochemistry and Biophysics, University of North Carolina Chapel Hill, NC 27514, USA., Franco E; Department of Mechanical Engineering, University of California, Riverside, CA 92521, USA., Afonin KA; Nanoscale Science Program, Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
Jazyk: angličtina
Zdroj: Advanced functional materials [Adv Funct Mater] 2018 Nov 28; Vol. 28 (48). Date of Electronic Publication: 2018 Oct 09.
DOI: 10.1002/adfm.201805959
Abstrakt: 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.
Competing Interests: Conflict of Interest The authors declare no conflict of interest.
Databáze: MEDLINE
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