Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Khisamutdinov, Emil F.; Li, Hui; Jasinski, Daniel L.; Chen, Jiao; Fu, Jing; Guo, Peixuan

doi:10.1093/nar/gku516

Cited by 125 publications

(193 citation statements)

References 61 publications

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“…DNA and RNA nanostructures have been successfully used to deliver several nanoparticles, especially in targeting the stimulation of cellular immune response 35 or for gene silencing 36 . For instance, DNA structures were used to deliver gold nanoparticles or antibodies 3 , CpG 37 and doxorubicin 38 ; 10 nm-sized DNA tetrahedra were also used to deliver siRNA molecules 39 .…”

Section: Discussionmentioning

confidence: 99%

Programmable RNA microstructures for coordinated delivery of siRNAs

et al. 2016

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RNA is a natural multifunctional polymer, and is an essential component in both complex pathways and structures within the cellular environment. For this reason, artificial self-assembling RNA nanostructures are emerging as a powerful tool with broad applications in drug delivery and metabolic pathway regulation. To date, coordinated delivery of functional molecules via programmable RNA assemblies has been primarily done using nanosize RNA scaffolds. However, larger scaffolds could expand existing capabilities for spatial arrangement of ligands, and enable the controlled delivery of highly concentrated molecular loads. Here, we investigate whether micron-size RNA scaffolds can be assembled and further functionalized with different cargos (e.g. various siRNAs and fluorescent tags) for their synchronized delivery to diseased cells. Since known design approaches to build large RNA scaffolds are still underdeveloped, we apply, for the first time, a tiling method widely used in DNA nanotechnology. DNA tiles have been extensively used to build a variety of scalable and modular structures that are easily decorated with other ligands. Here, we adapt a double crossover (DX) DNA tile motif to design de novo DX RNA tiles that assemble and form lattices via programmed sticky end interactions. Because the assembly protocols used in DNA nanotechnology are not suitable for RNA assembly, we optimize them to guarantee high yield of RNA lattices. The resulting constructs are robust and modular with respect to the presence of distinct siRNAs and fluorophores. RNA tiles and lattices are successfully transfected in either human breast cancer or prostate cancer cells, where they efficiently knockdown the expression of target genes. Blood serum stability assays indicate that RNA lattices are more resilient to nuclease degradation when compared to individual tiles, thus making them better suited for therapeutic purposes. Overall, because of its design simplicity, we anticipate that this approach will be utilized for a wide range of applications in therapeutic RNA nanotechnology.

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Section: Discussionmentioning

confidence: 99%

Programmable RNA microstructures for coordinated delivery of siRNAs

et al. 2016

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“…13 The thermodynamically stable properties make the pRNA-3WJ motif an ideal building block for constructing various RNA nanoparticles for diverse applications in nanomedicine and nanotechnology. 23 A large number of other highly ordered RNA structures have been reported and shown to perform diverse biological functions. 24-32 …”

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confidence: 99%

Construction of RNA–Quantum Dot Chimera for Nanoscale Resistive Biomemory Application

Lee

Yagati

et al. 2015

ACS Nano

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RNA nanotechnology offer advantages to construct thermally and chemically stable nanoparticles with well-defined shape and structure. Here we report the development of an RNA-Qd (quantum dot) chimera for resistive biomolecular memory application. Each Qd holds two copies of the pRNA three-way junction (pRNA-3WJ) of bacteriophage phi29 DNA-packaging motor. The fixed quantity of two RNA per Qd was achieved by immobilizing pRNA-3WJ harboring Sephadex aptamer for resin binding. Two thiolated pRNA-3WJ serves as two feet of the chimera to stand on the gold plate. The RNA nanostructure served as both an insulator and a mediator to provide defined distance between Qd and gold. Immobilization of chimera nanoparticle was confirmed through scanning tunneling microscopy (STM). As revealed by scanning tunneling spectroscopy (STS), the conjugated pRNA-3WJ-Qd chimera exhibited excellent electrical bi-stability signal for biomolecular memory function, demonstrating great potential for the development of resistive biomolecular memory and nanobio-inspired electronic device for information processing and computing.

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“…RNA nanotechnology is an emerging field with increasing popularity among the scientific community [13,21,[51][52][53][54][55][56][57][58][59]. RNA 3WJ-based nanoparticles have been successfully fabricated ( Fig.…”

Section: Discussionmentioning

confidence: 99%

RNA Nanoparticles Derived from Three-Way Junction of Phi29 Motor pRNA Are Resistant to I-125 and Cs-131 Radiation

Lihui

Rychahou

CuiZheng

et al. 2015

Nucleic Acid Therapeutics

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Radiation reagents that specifically target tumors are in high demand for the treatment of cancer. The emerging field of RNA nanotechnology might provide new opportunities for targeted radiation therapy. This study investigates whether chemically modified RNA nanoparticles derived from the packaging RNA (pRNA) threeway junction (3WJ) of phi29 DNA-packaging motor are resistant to potent I-125 and Cs-131 radiation, which is a prerequisite for utilizing these RNA nanoparticles as carriers for targeted radiation therapy. pRNA 3WJ nanoparticles were constructed and characterized, and the stability of these nanoparticles under I-125 and Cs-131 irradiation with clinically relevant doses was examined. RNA nanoparticles derived from the pRNA 3WJ targeted tumors specifically and they were stable under irradiation of I-125 and Cs-131 with clinically relevant doses ranging from 1 to 90 Gy over a significantly long time up to 20 days, while control plasmid DNA was damaged at 20 Gy or higher.

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Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles

Cited by 125 publications

References 61 publications

Programmable RNA microstructures for coordinated delivery of siRNAs

Programmable RNA microstructures for coordinated delivery of siRNAs

Construction of RNA–Quantum Dot Chimera for Nanoscale Resistive Biomemory Application

RNA Nanoparticles Derived from Three-Way Junction of Phi29 Motor pRNA Are Resistant to I-125 and Cs-131 Radiation

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