Electro-transfer of small interfering RNA ameliorated arthritis in rats

Inoue, Akira; Takahashi, Kenji; Mazda, Osam; Terauchi, Ryu; Arai, Yuji; Kishida, Tsunao; Shin‐Ya, Masaharu; Asada, Hidetsugu; Morihara, Toru; Tonomura, Hitoshi; Ohashi, Suzuyo; Kajikawa, Yoshiteru; Kawahito, Yutaka; Imanishi, Jirô; Kawata, Mitsuhiro; Kubo, Toshikazu

doi:10.1016/j.bbrc.2005.08.198

Cited by 60 publications

(54 citation statements)

References 31 publications

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“…Nonviral transfection with synthetic siRNA is free from virusassociated adverse effects, while the RNAi effect may be transient. 43,53,54 Although the most appropriate delivery system should be selected for each RNAi therapeutic application, electrotransfer of synthetic siRNA may be suitable for Mitf-knockdown therapy for melanoma, because long-lasting silencing effects are not always required to kill tumor cells that have been successfully transfected with siRNA.…”

Section: Discussionmentioning

confidence: 99%

“…53 We also employed electroporation to therapeutic RNAi for rheumatoid arthritis in rat, indicating that the articular disorder was drastically ameliorated by silencing tumor necrosis factor-a in inflammatory sinovial tissue. 43 An advantage of electroporation is that the siRNA can be exclusively introduced into the cells that reside in the portion between the electrodes. Electroporation has been clinically used to administer chemotherapeutic agents into tumors of patients, who suffer from head and neck carcinomas, 63 basal cell carcinomas 64,65 as well as malignant melanoma (electrochemotherapy), 64,66 demonstrating that electroporation can be safely applied to patients.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

et al. 2006

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Microphthalmia-associated transcription factor (Mitf) is critically involved in melanin synthesis as well as differentiation of cells of the melanocytic lineage. Some earlier studies suggested that Mitf is also essential in the survival of melanoma cells, but this notion remains controversial. We synthesized short interfering RNA (siRNA) duplexes corresponding to the mitf sequence and transfected them into B16 melanoma. Lipid-mediated transfection in vitro of Mitfspecific siRNA resulted in specific downregulation of Mitf and of the tyrosinase that is a transcriptional target of Mitf. This treatment also remarkably reduced the viability of melanoma cells by inducing apoptosis. To examine the potential feasibility of RNAi therapy against melanoma, B16 cells were subcutaneously injected into syngenic mice and siRNA was transfected into the pre-established tumor by means of electroporation. The Mitf-specific siRNA drastically reduced outgrowth of subcutaneous melanoma, while nonspecific siRNA failed to affect tumor progression. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-based analysis of tumor specimens demonstrated that the tumor cells transfected with Mitf-siRNA effectively underwent apoptosis in vivo. The present results indicate that Mitf plays important roles in melanoma survival. Intratumor electrotransfer of Mitf-specific siRNA may provide a powerful strategy for therapeutic intervention of malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

et al. 2006

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“…In rodents, EP have been used to deliver siRNAs in various organs such as skin, 29 eyes, 30 brain, 31 muscles, 32,33 joint tissue 34,35 and kidney. 36 However, delivery of large nucleic acids (plasmids) have been found to be poorly efficient in solid tumors.…”

Section: Introductionmentioning

confidence: 99%

In vivo gene silencing in solid tumors by targeted electrically mediated siRNA delivery

et al. 2007

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“…The potential application of RNAi-based therapy in rheumatoid disorders is evaluated. The effects that TNF-a was silenced by local and systemic delivery of siRNA have been evaluated in experimental arthritic models (Inoue et al, 2005;Schiffelers et al, 2005). The siRNA designed to silence TNF-a, was delivered into joints by electroporation against experimental arthritis in animal models and strongly inhibited joint inflammation by inhibition of the expression of TNF-a.…”

Section: Discussionmentioning

confidence: 99%

The role of Act1, a NF-κB-activating protein, in IL-6 and IL-8 levels induced by IL-17 stimulation in SW982 cells

Song

Wang

et al. 2013

Pharmaceutical Biology

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Context: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation in the synovial membrane of affected joints. It has been shown that several kinds of cytokine were increased in synovial fluid, while the underlying mechanism remains poorly understood. Objectives: NF-kB activator 1 (Act1) is a recently identified protein binding to the IkB kinase complex. Our study aimed to investigate the expression of Act1 induced by cytokine IL-17 stimulation in SW982 cells. Materials and methods:The human synovial sarcoma cell line SW982 and primary cultured RA fibroblast-like synovial cells were used. RT-PCR and Western blot assays were selected to investigate the genetic and protein expression of Act1. Additionally, four independent Act1 small interfering RNA (siRNA) oligonucleotides were designed and obtained according to the GenBank cDNA, the sequence of Act1 (Traf3ip2). Finally, enzyme-linked immunosorbent assay (ELISA) double antibody sandwich was used to assay supernatant IL-6 and IL-8 concentrations.Results: The Act1 mRNA expression level increased significantly after stimulation with IL-17 (5-100 ng/ml) in SW982 cells. Additionally, the level of Act1 mRNA expression correlated positively with the concentration of IL-17 (p50.01). IL-17 induced IL-6 and IL-8 in SW982 cells was in a concentration-and time-dependent way. Furthermore, ELISA assay revealed that IL-17 (20 ng/ml) significantly increased IL-6 (1927.4 AE 288.77 versus 786.5 AE 172.42 ng/ml, p50.01) and IL-8 levels (984.8 AE 95.09 ng/ml versus 307.1 AE 90.83 ng/ml, p50.01) compared with control group after stimulation for 24 h. However, transfection of Traf3ip2 siRNA markedly decreased IL-6 (995.9 AE 115.30 ng/ml versus 1816.1 AE 273.27 ng/ml, p50.01) and IL-8 levels (575.6 AE 65.96 ng/ml versus 929.4 AE 124.39 ng/ml, p50.01) compared to transfection negative control. These findings suggested that IL-6 and IL-8 level induced by IL-17 in SW982 cells could be reversed by down-regulation of Act1 expression level with Traf3ip2 siRNA. Conclusion: Our results suggested that Act1 might play a key role in the pathophysiology and the treatment of RA.

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Electro-transfer of small interfering RNA ameliorated arthritis in rats

Cited by 60 publications

References 31 publications

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

Therapeutic RNA interference of malignant melanoma by electrotransfer of small interfering RNA targeting Mitf

In vivo gene silencing in solid tumors by targeted electrically mediated siRNA delivery

The role of Act1, a NF-κB-activating protein, in IL-6 and IL-8 levels induced by IL-17 stimulation in SW982 cells

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