RNAi in Clinical Studies

Kubowicz, P.; Zelaszczyk, D.; Pekala, E.

doi:10.2174/09298673113209990118

Cited by 56 publications

(40 citation statements)

References 132 publications

(149 reference statements)

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“…For example, small interference RNA (siRNA), short hairpin RNA, and microRNA are broadly used to induce targeted gene silencing for the treatment of cancers [1]. RNA aptamers targeting coagulation, complement, and vasculogenesis are currently undergoing clinical trials for thrombotic disorder and macular degeneration [2].…”

mentioning

confidence: 99%

2′Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors

Lee

Urban

et al. 2016

Nucleic Acid Therapeutics

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Although the use of RNAs has enormous therapeutic potential, these RNA-based therapies can trigger unwanted inflammatory responses by the activation of pattern recognition receptors (PRRs) and cause harmful side effects. In contrast, the immune activation by therapeutic RNAs can be advantageous for treating cancers. Thus, the immunogenicity of therapeutic RNAs should be deliberately controlled depending on the therapeutic applications of RNAs. In this study, we demonstrated that RNAs containing 2¢fluoro (2¢F) pyrimidines differentially controlled the activation of PRRs. The activity of RNAs that stimulate toll-like receptors 3 and 7 was abrogated by the incorporation of 2¢F pyrimidine. By contrast, incorporation of 2¢F pyrimidines enhanced the activity of retinoic acid-inducible gene 1-stimulating RNAs. Furthermore, we found that transfection with RNAs containing 2¢F pyrimidine and 5¢ triphosphate (5¢ppp) increased cell death and interferon-b expression in human cancer cells compared with transfection with 2¢hydroxyl 5¢ppp RNAs, whereas RNAs containing 2¢O-methyl pyrimidine and 5¢ppp completely abolished the induction of cell death and cytokine expression in the cells. Our findings suggest that incorporation of 2¢F and 2¢O-methyl nucleosides is a facile approach to differentially control the ability of therapeutic RNAs to activate or limit immune and inflammatory responses depending on therapeutic applications.

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mentioning

confidence: 99%

2′Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors

Lee

Urban

et al. 2016

Nucleic Acid Therapeutics

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“…The actions of miRNAs and siRNAs may be unified as RNA interference (RNAi) process that silences target gene expression in a sequence dependent manner in cells, [15][16][17] yet their specific mechanisms may differ ( Fig. 1).…”

Section: Mechanistic Actions and Therapeutic Potentials Of Sirnas Andmentioning

confidence: 99%

Bioengineered non-coding RNA agent (BERA) in action

Duan

2016

Bioengineered

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Non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and small interfering RNAs (siRNAs) are important players in the control of gene regulation and represent novel promising therapeutic targets or agents for the treatment of various diseases. While synthetic ncRNAs are predominately utilized, the effects of excessive artificial modifications on higher-order structures, activities and toxicities of ncRNAs remain uncertain. Inspired by recombinant protein technology allowing large-scale bioengineering of proteins for research and therapy, efforts have been made to develop practical and effective means to bioengineer ncRNA agents. The fermentation-based approaches shall offer biological ncRNA agents with natural modifications and proper folding critical for ncRNA structure, function and safety. In this article, we will summarize current recombinant RNA platforms to the production of ncRNA agents including siRNAs and miRNAs. The applications of bioengineered ncRNA agents for basic research and potential therapeutics are also discussed.

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“…RNA interference (RNAi) is a powerful gene-silencing process that holds great promise in the field of gene therapy [1]. The liver is an important organ with a number of potential therapeutic siRNA targets, including cholesterol biosynthesis, fibrosis, hepatitis and hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Optimization of siRNA Delivery Method into the Liver by Sequential Injection of Polyglutamic Acid and Cationic Lipoplex

Hattori¹,

Arai²,

Kikuchi³

et al. 2015

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Previously, we developed a novel siRNA transfer method to the liver by sequential intravenous injection of poly-L-glutamic acid (PGA) and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the charge ratio (+/−) of cationic liposome/siRNA, molecular weight of PGA and cationic lipid of cationic liposome on the biodistribution of siRNA after sequential injection of PGA plus cationic lipoplex. When 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (Chol) lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when DOTAP/Chol lipoplex was intravenously injected at 1 min after intravenous injection of PGA, siRNA was largely accumulated in the liver

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RNAi in Clinical Studies

Cited by 56 publications

References 132 publications

2′Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors

2′Fluoro Modification Differentially Modulates the Ability of RNAs to Activate Pattern Recognition Receptors

Bioengineered non-coding RNA agent (BERA) in action

Optimization of siRNA Delivery Method into the Liver by Sequential Injection of Polyglutamic Acid and Cationic Lipoplex

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