RNAi‐Microsponges Form through Self‐Assembly of the Organic and Inorganic Products of Transcription

Shopsowitz, Kevin E.; Roh, Young Hoon; Deng, Zhou J.; Morton, Stephen W.; Hammond, Paula T.

doi:10.1002/smll.201302676

Cited by 100 publications

(95 citation statements)

References 41 publications

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“…It was previously shown that long ssRNA molecules generated by RCA can form composite nanoparticles consisting of nucleic acids and magnesium pyrophosphate. 30 To better understand the structure of our DNFs, we used energy dispersive X-ray spectroscopy to analyze their elemental composition (Figure 2g). Energy dispersive X-ray spectroscopy confirmed the presence of nitrogen, oxygen, magnesium and phosphorus, which reveals that the DNFs are composed of DNA and magnesium pyrophosphate.…”

Section: Construction and Characterization Of The Dnfsmentioning

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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Section: Construction and Characterization Of The Dnfsmentioning

confidence: 99%

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Jin

Liu

et al. 2017

NPG Asia Mater

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“…Inter-and intramolecular hybridizations tend to fold these linear chains into particles with the size affected by factors such as the selection [4,7] and concentration [8] of the polymerases, the elongation time [9] and so on. The magnesium pyrophosphate generated during the synthesis process, as a side product of the polymerized nucleotides, was recently reported to be necessary for the structural integrity of the nucleic acid particles [7,10]. In the pioneering work demonstrated by Hammond and coworkers, RNA microparticles composed of concatenated siRNA (more than half a million repeats per particle) were developed for siRNA delivery [2].…”

Section: Rcr Product Self-assembled Micro-nanoparticlesmentioning

confidence: 99%

Rolling Circle Replication for Engineering Drug Delivery Carriers

Sun

Lü

2015

Ther. Deliv.

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The technique to generate long concatenated nucleic acids capable of constructing nano-, micro-and macro-scopic structures is a powerful platform for designing drug d elivery carriers.Rolling circle replication (RCR), including DNA and RNA replication, is a process found in some bacteriophages or viroids for replicating the DNA or RNA genomes. In vitro versions of this natural phenomenon are the rolling circle amplification (RCA) [1] and rolling circle transcription (RCT) [2] that enabled cost-efficient synthesis of concatenated DNA and RNA. Φ29 DNA polymerase, the most popular DNA polymerase for RCA, is capable to replicating the full-length genome of Φ29 bacteriophage [3]. The superb RCA performance of Φ29 DNA polymerase is attributed to its high processivity and strand displacement ability, making it possible to generate long consecutive DNA products even in the presence of topologically complicated DNA templates. In addition, Φ29 DNA polymerase reacts in an isothermal condition that obviates the need for a thermal cycler for the reaction. Other isothermal polymerases that can be employed in RCA include Bst DNA polymerase [4], Vent exo-DNA polymerase [1] and so on. For a typical RCA, the three major components are the DNA polymerase, a single stranded DNA (ssDNA) template and a ssDNA primer. The fact that the product is an amplification of the ssDNA template leads to extensive study of RCA for signal amplification in biodetection [1]. Recently, the polymeric property of RCA products has attracted a lot of attention due to the development of DNA nanotechnology [5]. The programmability of the DNA template makes RCA a highly versatile platform to generate DNA particles or gels for biomedical applications. Functional DNA sequences, such as aptamers and DNAzymes, can be incorporated into the RCA products for applications including targeted drug delivery or bioimaging.Similar to RCA, RCT generates periodic RNA products from a ssDNA template. A typical RCT reaction requires only two major components, a DNA-dependent RNA polymerase (generally T7 RNA polymerase) and a ssDNA template containing the binding site of the RNA polymerase [2]. The high programmability of the DNA template makes RCT easy to manipulate. The flexible base-pairing rules of RNA, such as noncanonical base pairing, make RNA nanostructures more versatile and thermally stable than their DNA counterparts, giving RNA protein-like diversity in functions [6]. Functional RNA molecules such as aptamers, ribozyme, miRNA and siRNA have greatly expanded the toolbox for designing RNA carriers for drug delivery.In this editorial, we highlight recent advances in using RCR techniques for engineering DNA-and RNA-based carriers for

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“…Our strategy for developing Multi‐RNAi‐MSs as a drug‐delivery platform involved an additional condensation step by electrostatic interactions and physical agitation 5, 6, 7. In this study, positively charged linear polyethylenimine (PEI) was chosen to achieve effective intracellular uptake and endosomal escape.…”

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confidence: 99%

A Multi‐RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs

et al. 2015

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Packaging multiple small interfering RNA (siRNA) molecules into nanostructures at precisely defined ratios is a powerful delivery strategy for effective RNA interference (RNAi) therapy. We present a novel RNA nanotechnology based approach to produce multiple components of polymerized siRNA molecules that are simultaneously self‐assembled and densely packaged into composite sponge‐like porous microstructures (Multi‐RNAi‐MSs) by rolling circle transcription. The Multi‐RNAi‐MSs were designed to contain a combination of multiple polymeric siRNA molecules with precisely controlled stoichiometry within a singular microstructure by manipulating the types and ratios of the circular DNA templates. The Multi‐RNAi‐MSs were converted into nanosized complexes by polyelectrolyte condensation to manipulate their physicochemical properties (size, shape, and surface charge) for favorable delivery, while maintaining the multifunctional properties of the siRNAs for combined therapeutic effects. These Multi‐RNAi‐MS systems have great potential in RNAi‐mediated biomedical applications, for example, for the treatment of cancer, genetic disorders, and viral infections.

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RNAi‐Microsponges Form through Self‐Assembly of the Organic and Inorganic Products of Transcription

Cited by 100 publications

References 41 publications

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Biodegradable, multifunctional DNAzyme nanoflowers for enhanced cancer therapy

Rolling Circle Replication for Engineering Drug Delivery Carriers

A Multi‐RNAi Microsponge Platform for Simultaneous Controlled Delivery of Multiple Small Interfering RNAs

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