An RNA Aptamer Capable of Forming a Hydrogel by Self-Assembly

Huang, Zhen; Kangovi, Gagan N.; Wen, Wei; Lee, Sangwoo; Niu, Li

doi:10.1021/acs.biomac.7b00314

Cited by 13 publications

(13 citation statements)

References 60 publications

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“…[ 7,16 ] Moreover, a new attempt has been proposed for production of pure RNAs, which are intended to facilitate RNA research without exogenous substances but have no programmed function. [ 14 ]…”

Section: Discussion and Perspectivementioning

confidence: 99%

“…[8][9][10][11][12][13] To resolve the shortcomings of single RNA nanomaterials, few attempts have been made to develop macroscopic RNA moieties to identify them as functional mimics with a wide range of applications such as delivery vehicles for cancer therapy and cell signal sensing. [14][15][16][17] Several polymeric-nucleic acid hybrids have been discovered but they cannot overcome the additional conjugation steps or postfunctionalization methods resulting in decreased efficiency and lower cost effectiveness. [18] Here, we demonstrate a simple and integrated RNA hydrogel made of structurally long RNA that can articulate function without extraneous support.…”

mentioning

confidence: 99%

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Protein‐Encoding Free‐Standing RNA Hydrogel for Sub‐Compartmentalized Translation

Ahn¹,

Kim²,

Vellampatti³

et al. 2022

Advanced Materials

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ability of RNA moieties to serve both as a genetic source code and as a catalytic repertoire suggests them as excellent drug targets, beyond their use as a behavioral blueprint for regulatory protein production. Despite their role, single RNA has limited practical applications due to its intrinsic thermodynamic and chemical instability, the small scale of production facilities, lack of available toolkits, difficulty in structure and stability predictions. [8][9][10][11][12][13] To resolve the shortcomings of single RNA nanomaterials, few attempts have been made to develop macroscopic RNA moieties to identify them as functional mimics with a wide range of applications such as delivery vehicles for cancer therapy and cell signal sensing. [14][15][16][17] Several polymeric-nucleic acid hybrids have been discovered but they cannot overcome the additional conjugation steps or postfunctionalization methods resulting in decreased efficiency and lower cost effectiveness. [18] Here, we demonstrate a simple and integrated RNA hydrogel made of structurally long RNA that can articulate function without extraneous support. DNA templates programmed with the G-quadruplex structural and purposeful motif were used to form a function-encoding, free-standing RNA hydrogel. Multivalent electrostatic interactions of the G-quadruplexes (G4) in RNA can self-fold into complex structures that can serve as major biological regulators in protein synthesis and in catalysis. Due to the abundance of structural primitives and functional diversity, RNA has been utilized for designing nature-defined goals despite its intrinsic chemical instability and lack of technologies. Here, a robust, free-standing RNA hydrogel is developed through a sequential process involving both ligation and rolling circle transcription to form RNA G-quadruplexes, capable of both catalytic activity and enhancing expression of several proteins in sub-compartmentalized, phase-separated translation environments. The observations suggest that this hydrogel will expand RNA research and impact practical RNA principles and applications.

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Section: Discussion and Perspectivementioning

confidence: 99%

mentioning

confidence: 99%

Protein‐Encoding Free‐Standing RNA Hydrogel for Sub‐Compartmentalized Translation

Ahn¹,

Kim²,

Vellampatti³

et al. 2022

Advanced Materials

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“…This will improve the therapeutic effect and simultaneously reduce the dose required, and thus reduce off‐target effects . Recently, more and more effort has been directed towards local delivery of RNA‐based drugs for several different disease models . In the case of local delivery, retention at the administration site can be improved by encapsulation of RNAi compounds in controlled drug delivery systems such as hydrogels.…”

Section: Introductionmentioning

confidence: 99%

“…[10] Recently,m ore and more effort has been directedt owardsl ocal delivery of RNA-basedd rugs for several different disease models. [11][12][13][14][15][16][17][18] In the case of local delivery,r etention at the administrationsite can be improvedbyencapsulation of RNAic ompounds in controlled drug delivery systems such as hydrogels. These systemss houldf ulfill various requirements with respect to biocompatibility,i njectability,a nd control over drug release profiles.…”

Section: Introductionmentioning

confidence: 99%

Controlled Release of RNAi Molecules by Tunable Supramolecular Hydrogel Carriers

Bakker

Rooij

Dankers

2018

Chemistry An Asian Journal

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Local, sustained release and presentation of RNAi therapeutics can be achieved with hydrogel delivery systems. Here we show the development of a supramolecular hydrogel into a local RNAi delivery system. By careful material design, two simple but effective strategies are introduced to obtain controlled release of two classes of RNAi therapeutics, that is, microRNA and antimiR. It was shown that the release of microRNA could be regulated using cholesterol-modification for interaction with the supramolecular hydrogel. Non-modified antimiR release could be controlled via supramolecular introduction of positively charged additive molecules into the supramolecular hydrogel. In this way, either the cholesterol-modification on the drug or the charge introduction into the hydrogel provides handles for controlled RNAi therapy.

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“…Researchers have focused largely on engineering RNA because of their numerous biological functions including storage of genetic information, regulation of target gene and transfer of molecules. Various technologies have been applied to produce RNA‐based structures to utilize the biological features of RNA . In particular, rolling circle transcription (RCT) has been used extensively to generate RNA structures with increased loading capacity and efficacy of therapeutic RNA .…”

mentioning

confidence: 99%

Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands

Kim

Han

et al. 2019

Adv Healthcare Materials

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COMMUNICATION (1 of 7)such as gene therapy, [2] targeted drug delivery, [3] and biomolecular imaging. [4] Researchers have focused largely on engineering RNA because of their numerous biological functions including storage of genetic information, regulation of target gene and transfer of molecules. Various technologies have been applied to produce RNA-based structures to utilize the biological features of RNA. [5] In particular, rolling circle transcription (RCT) has been used extensively to generate RNA structures with increased loading capacity and efficacy of therapeutic RNA. [6] In a recent study, gene regulation using an RCT-based RNA nanoball showed therapeutic potential for treatment of agerelated macular degeneration. [7] On the other hand, specific sequences or structures of RNA are known to stimulate immune responses. [8] While the aforementioned RNAs can be utilized for boosting immune responses, [9] there are concerns that the RNA-based structures may cause undesired immune activation, which could greatly limit their therapeutic efficacy. [10] To address the issue, there have been efforts to circumvent the immune systems through chemically modified RNA. [11] On the other hand, the immunogenicity of self-assemblies composed of DNA, RNA, [12] or DNA-RNA hybrid [13] has been investigated widely for the better understanding of immunogenic properties of nucleic acid-based structures and their clinical translation. However, the study of immune stimulating properties of self-assembled RNA particles with potentially immunostimulatory RNA fabricated from RCT is not well established, whereas DNA particles from rolling circle amplification have been widely exploited as adjuvants for boosting immune response. [14] In order to clinically translate the fast-evolving RNA-based therapeutics, evaluation of immune response to self-assembled RNA particles is indispensable.In this study, possible immunostimulatory effect of RNA microspheres (RMSs) depending on the sequences or structures of RNA was fully investigated. The RMSs are made up of tandem copies of RNA strands self-assembled by RCT. [6a] The RMSs exhibited an enhanced resistance to serum nucleases, which could enhance the cellular uptake efficiency, while effectively releasing RNA strands under lysosome-mimetic Self-assembled RNA particles have been exploited widely to maximize the therapeutic potential of RNA. However, the immune response via RNA particles is not fully understood. In addition, the investigation of the immunogenicity from RNA-based particles is required owing to inherent immunostimulatory effects of RNA for clinical translation. To examine the immune stimulating potency, rationally designed microsized RNA particles, called RNA microspheres (RMSs), are generated with single or double strands via rolling circle transcription. The RMSs show an exceptional stability in the presence of serum, while they are selectively degraded under endolysosomal conditions. With precisely controlled size, both RMSs are successfully taken up by macrophages....

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An RNA Aptamer Capable of Forming a Hydrogel by Self-Assembly

Cited by 13 publications

References 60 publications

Protein‐Encoding Free‐Standing RNA Hydrogel for Sub‐Compartmentalized Translation

Protein‐Encoding Free‐Standing RNA Hydrogel for Sub‐Compartmentalized Translation

Controlled Release of RNAi Molecules by Tunable Supramolecular Hydrogel Carriers

Immunostimulatory Effects Triggered by Self‐Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands

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