Multifunctional RNA Nanoparticles

Afonin, Kirill A.; Viard, Mathias; Koyfman, Alexey Y.; Martins, Angélica N.; Kasprzak, Wojciech K.; Panigaj, Martin; Desai, Ravi A.; Santhanam, Arti; Grabow, Wade W.; Jaeger, Luc; Heldman, Eliahu; Reiser, Jakob; Chiu, Wah; Freed, Eric O.; Shapiro, Bruce A.

doi:10.1021/nl502385k

Cited by 186 publications

(214 citation statements)

References 64 publications

(124 reference statements)

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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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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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“…Previous research efforts have seen the incorporation of multiple RNA functional modules within RNA nanoparticles, resulting in the generation of singular entities that harbor multiple distinct functionalities [9,10]. This same approach could also be applied to the modular functional elements themselves.…”

Section: Vision Papermentioning

confidence: 99%

RNA Toehold Interactions Initiate Conditional Gene Silencing

Zakrevsky¹,

Bindewald²,

Shapiro³

2016

DNA and RNA Nanotechnology

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“…The simultaneous introduction of multiple RNAi inducers targeting different genes in conjunction with other functional moieties (therapeutic aptamers, ribozymes, fluorescent dyes, peptides or small molecules) may maximize the synergistic therapeutic effect [35][36][37][38][39][40]. Precise control over the composition and stoichiometry of these combinatorial drugs is essential to guarantee the consistency in batch-to-batch formulations [32].…”

Section: Multifunctional Rna and Dna Nanoparticlesmentioning

confidence: 99%

“…One of the strategies, called RNA architectonics, uses tecto-RNAs [47][48][49][50] that combine different RNA three-dimentional building blocks (called motifs) allowing remarkable structural control in bottom-up assembly . In particular, computationally designed [72] and experimentally tested [32,35,73,74] nanorings take advantage of the so-called RNA kissing loop ineracting motifs (Figure 1, case 4). Other examples use the structural motifs extracted from the phage phi29 pRNAs [75] that were widely used in the engineering of multiple stable and functional RNA nanoscaffolds [76][77][78][79][80][81][82][83][84][85][86][87].…”

Section: Multifunctional Rna and Dna Nanoparticlesmentioning

confidence: 99%

Triggering RNAi with multifunctional RNA nanoparticles and their delivery

Dao¹,

Viard²,

Martins³

et al. 2015

DNA and RNA Nanotechnology

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in the bloodstream, poor cellular uptake, and inefficient intracellular release. In an attempt to solve these issues, different types of RNAi therapeutic delivery strategies including multifunctional RNA nanoparticles are being developed. In this mini-review, we will briefly describe some of the current approaches.Keywords: RNA nanotechnology, RNA nanoparticles, RNA/DNA hybrids, RNA interference, siRNA, delivery IntroductionAccording to the Social Security Administration, average Americans that reach age 65 today most likely will live to be 84 years old [1]. However, with older age, the chances of contracting deadly diseases, such as cancer, increases dramatically. Some cancers (e.g. breast cancer) can be removed surgically but this does not guarantee that the disease will not return within a patient's lifetime. For other types of cancer (e.g. chronic lymphocytic leukemia), surgery may have very little effect (http://www. cancer.org). Other available treatments are chemo-and immunotherapies. However, these alternatives lack target specificity and cause severe toxic side effects affecting the growth of hair, nails, loss of appetite and blood cell count, just to name a few (http://www.cancer.org). Therefore, the advancements in biomedical technologies that provide safe and effective cancer treatment are in demand. Among the novel approaches is the recognition and use of specific intracellular RNA signatures (e.g. an overexpression of certain genes) that are especially important in detection and personalized treatments of cancers as well as viral infections, and autoimmune diseases [2][3][4]. The wide use of novel therapeutics based on target specific RNA-mediated gene silencing, called RNA interference or RNAi, will likely become the next breakthrough in cancer therapy. The first successful therapeutic knockdown of the endogenous gene, apolipoprotein B (ApoB), occurred in a 2004 study [5], only a few years after the original discovery of RNAi [6]. In 2010, DOI 10.1515/rnan-2015-0001 Received April 6, 2015 accepted May 6, 2015 Abstract: Proteins are considered to be the key players in structure, function, and metabolic regulation of our bodies. The mechanisms used in conventional therapies often rely on inhibition of proteins with small molecules, but another promising method to treat disease is by targeting the corresponding mRNAs. In 1998, Craig Mellow and Andrew Fire discovered dsRNA-mediated gene silencing via RNA interference or RNAi. This discovery introduced almost unlimited possibilities for new gene silencing methods, thus opening new doors to clinical medicine. RNAi is a biological process that inhibits gene expression by targeting the mRNA. RNAi-based therapeutics have several potential advantages (i) a priori ability to target any gene, (ii) relatively simple design process, (iii) sitespecificity, (iv) potency, and (v) a potentially safe and selective knockdown of the targeted cells. However, the problem lies within the formulation and delivery of RNAi therapeutics including rapid excretion, instab...

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Multifunctional RNA Nanoparticles

Cited by 186 publications

References 64 publications

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

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

RNA Toehold Interactions Initiate Conditional Gene Silencing

Triggering RNAi with multifunctional RNA nanoparticles and their delivery

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