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.
| Original language | English (US) |
|---|---|
| Article number | 1805959 |
| Journal | Advanced Functional Materials |
| Volume | 28 |
| Issue number | 48 |
| DOIs | |
| State | Published - Nov 28 2018 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Materials Science(all)
- Condensed Matter Physics
Cite this
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RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition. / 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; Vivero-Escoto, Juan; Johnson, Peter F.; Dobrovolskaia, Marina A.; Dokholyan, Nikolay V.; Franco, Elisa; Afonin, Kirill A.
In: Advanced Functional Materials, Vol. 28, No. 48, 1805959, 28.11.2018.Research output: Contribution to journal › Article
TY - JOUR
T1 - RNA Fibers as Optimized Nanoscaffolds for siRNA Coordination and Reduced Immunological Recognition
AU - Rackley, Lauren
AU - Stewart, Jaimie Marie
AU - Salotti, Jacqueline
AU - Krokhotin, Andrey
AU - Shah, Ankit
AU - Halman, Justin R.
AU - Juneja, Ridhima
AU - Smollett, Jaclyn
AU - Lee, Lauren
AU - Roark, Kyle
AU - Viard, Mathias
AU - Tarannum, Mubin
AU - Vivero-Escoto, Juan
AU - Johnson, Peter F.
AU - Dobrovolskaia, Marina A.
AU - Dokholyan, Nikolay V.
AU - Franco, Elisa
AU - Afonin, Kirill A.
PY - 2018/11/28
Y1 - 2018/11/28
N2 - 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.
AB - 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.
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U2 - 10.1002/adfm.201805959
DO - 10.1002/adfm.201805959
M3 - Article
AN - SCOPUS:85055680172
VL - 28
JO - Advanced Functional Materials
JF - Advanced Functional Materials
SN - 1616-301X
IS - 48
M1 - 1805959
ER -