Self-assembled RNA interference microsponges for efficient siRNA delivery

Lee, Jong Bum; Hong, Jinkee; Bonner, Daniel K.; Poon, Zhiyong; Hammond, Paula T.

doi:10.1038/nmat3253

Cited by 448 publications

(393 citation statements)

References 35 publications

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“…The TEM and SEM analysis revealed individual, densely packed nanoparticles of uniform size and a petal‐like surface structure (Figure 3 c and 3 d). Similar crystalline‐like, globular microstructures were recently generated from short, circular DNA13 and RNA14 templates. Nevertheless, despite detailed microscopic characterization of these DNA/RNA microstructures, the importance of pyrophosphate:magnesium complexes for the nucleation and condensation process remained unappreciated.…”

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confidence: 70%

DNA Nanoparticles for Improved Protein Synthesis In Vitro

et al. 2016

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The amplification and digital quantification of single DNA molecules are important in biomedicine and diagnostics. Beyond quantifying DNA molecules in a sample, the ability to express proteins from the amplified DNA would open even broader applications in synthetic biology, directed evolution, and proteomics. Herein, a microfluidic approach is reported for the production of condensed DNA nanoparticles that can serve as efficient templates for in vitro protein synthesis. Using phi29 DNA polymerase and a multiple displacement amplification reaction, single DNA molecules were converted into DNA nanoparticles containing up to about 104 clonal gene copies of the starting template. DNA nanoparticle formation was triggered by accumulation of inorganic pyrophosphate (produced during DNA synthesis) and magnesium ions from the buffer. Transcription–translation reactions performed in vitro showed that individual DNA nanoparticles can serve as efficient templates for protein synthesis in vitro.

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confidence: 70%

DNA Nanoparticles for Improved Protein Synthesis In Vitro

et al. 2016

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“…In addition, they can be endowed with diverse properties, including biorecognition, sensing and imaging, by either hybridizing with complementary oligonucleotides tethered to functional moieties or programming a functional sequence into the DNA chain. [18][19][20][21][22][23] Herein, we present a biodegradable cancer therapeutic system with multiple built-in functions for targeted dual gene silencing and cancer therapy by using a rolling circle amplification (RCA) method (Figure 1). Through the smart design of the template DNA sequence, AS1411 aptamer, an early growth response-1 (EGR-1) DNAzyme, and a survivin DNAzyme were simultaneously incorporated into a self-assembly DNA nanoflower (DNF), which was composed of a long single-stranded DNA (ssDNA) and magnesium pyrophosphate.…”

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confidence: 99%

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Jin

Liu

et al. 2017

NPG Asia Mater

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Safety and efficiency remain the critical hurdles hindering the practical application of gene agents, even though great effort has been made to develop various gene carriers. Herein, we present a novel biodegradable cancer therapeutic system based on DNA nanoflowers (DNFs) for targeted dual gene silencing. The therapeutic system was constructed by copying a rolling circle amplification template to produce long single-stranded DNAs with cell targeting and dual gene-silencing capability. The structure of the DNFs collapsed at acidic pH due to the decomposition of the co-assembled magnesium pyrophosphate, generating Mg 2+ ions that act as cofactors for the DNAzymes and increase their ability to recognize and cleave target mRNAs. In vitro and in vivo studies demonstrated that the multifunctional DNFs showed promise for targeted cancer cell recognition, gene silencing, induction of apoptosis and inhibition of tumor growth. Considering the enhanced therapeutic effect and biocompatibility of this therapeutic platform, it is anticipated to be of great interest for the clinical treatment of cancers.

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“…Although the Dicer‐mediated generation of siRNA from a RNAi microsponge was ≈21% in a previous study,8 the formulation of the nanostructure was modified recently to 2D sheets to provide the enzyme with a wide surface area 11. This approach improved the efficiency of Dicer cleavage significantly to more than 80%.…”

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confidence: 99%

Bubbled RNA‐Based Cargo for Boosting RNA Interference

et al. 2017

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As ribonucleic acid (RNA) nanotechnology has advanced, it has been applied widely in RNA‐based therapeutics. Among the range of approaches, enzymatically synthesized RNA structures for inducing RNA interference in cancer cells have potential for silencing genes in a target‐specific manner. On the other hand, the efficiency of gene silencing needs to be improved to utilize the RNA‐based system for RNAi therapeutics. This paper introduces a new approach for efficient generation of siRNA from bubbled RNA‐based cargo (BRC). The presence of bubbles in between to avoid nonfunctional short dsRNAs allows the RNA‐based cargoes to contain multiple Dicer‐cleavage sites to release the functional siRNAs when introduced to cells. BRCs can be synthesized easily in a one‐pot process and be purified by simple centrifugation. Furthermore, efficient target gene silencing by the bubbled structure is confirmed both in vitro and in vivo. Therefore, this bubbled RNA cargo system can be utilized for target‐specific RNAi therapeutics with high efficiency in the generation of functional siRNAs in the target cells.

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Self-assembled RNA interference microsponges for efficient siRNA delivery

Cited by 448 publications

References 35 publications

DNA Nanoparticles for Improved Protein Synthesis In Vitro

DNA Nanoparticles for Improved Protein Synthesis In Vitro

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Bubbled RNA‐Based Cargo for Boosting RNA Interference

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