Continuous in vivo RNA interference mediated CKIP-1 gene silencing in mouse and rat bone: Optimization for dosage and duration

Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S363 ◽  
Author(s):  
Baosheng Guo ◽  
Ge Zhang ◽  
Tao Tang ◽  
Heng Wu ◽  
Gang Li ◽  
...  
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Rat Bone

scholarly journals RNA interference-mediated gene silencing in murine T cells: in vitro and in vivo validation of proinflammatory target genes

2008 ◽  
Vol 6 (1) ◽  
pp. 3 ◽  
Author(s):  
Tatjana C Gust ◽  
Luisa Neubrandt ◽  
Claudia Merz ◽  
Khusru Asadullah ◽  
Ulrich Zügel ◽  
...  
Keyword(s):  
T Cells ◽  
Rna Interference ◽  
Gene Silencing ◽  
Target Genes ◽  
In Vivo Validation

scholarly journals Intronic MicroRNA (miRNA)

2006 ◽  
Vol 2006 ◽  
pp. 1-13 ◽  
Author(s):  
Shi-Lung Lin ◽  
Joseph D. Miller ◽  
Shao-Yao Ying
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Regulatory System ◽  
Fine Tuning ◽  
Messenger Rnas ◽  
Noncoding Dna ◽  
Protein Coding ◽  
C Elegans ◽  
Adult Mice

Nearly 97% of the human genome is composed of noncoding DNA, which varies from one species to another. Changes in these sequences often manifest themselves in clinical and circumstantial malfunction. Numerous genes in these non-protein-coding regions encode microRNAs, which are responsible for RNA-mediated gene silencing through RNA interference (RNAi)-like pathways. MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) with complete or partial complementarity, are useful for the design of new therapies against cancer polymorphisms and viral mutations. Currently, many varieties of miRNA are widely reported in plants, animals, and even microbes. Intron-derived microRNA (Id-miRNA) is a new class of miRNA derived from the processing of gene introns. The intronic miRNA requires type-II RNA polymerases (Pol-II) and spliceosomal components for their biogenesis. Several kinds of Id-miRNA have been identified inC elegans, mouse, and human cells; however, neither function nor application has been reported. Here, we show for the first time that intron-derived miRNAs are able to induce RNA interference in not only human and mouse cells, but in also zebrafish, chicken embryos, and adult mice, demonstrating the evolutionary preservation of intron-mediated gene silencing via functional miRNA in cell and in vivo. These findings suggest an intracellular miRNA-mediated gene regulatory system, fine-tuning the degradation of protein-coding messenger RNAs.

scholarly journals Oral RNA Interference Therapy for Celiac Disease using a Polymeric Microsphere Formulation

2021 ◽  
Author(s):  
Husain Z. Attarwala ◽  
Kanika Suri ◽  
Mansoor M. Amiji
Keyword(s):  
Celiac Disease ◽  
Immune System ◽  
Rna Interference ◽  
Gene Silencing ◽  
Therapeutic Strategy ◽  
Immune Cell ◽  
Tissue Transglutaminase ◽  
Poly I:C ◽  
Chronic Inflammatory Condition

Abstract Celiac disease is a chronic inflammatory condition characterized by activation of the immune system in response to deamidation of gluten peptides brought about by tissue transglutaminase-2 (TG2). Overexpression of interleukin-15 (IL-15) in the intestinal epithelium and the lamina propria leads to the dysregulation of the immune system, leading to epithelial damage. The goal of this study was to develop an RNA interference therapeutic strategy for celiac disease using a combination of TG2 and IL-15 gene silencing in the inflamed intestine. TG2 and IL-15 silencing siRNA sequences, along with scrambled control, were encapsulated in Nanoparticle-in-Microsphere Oral System (NiMOS) and administered in poly(I:C) mouse model of celiac disease. Single TG2 and IL-15 siRNA therapy as well the combination showed effective gene silencing in vivo. Additionally, it was found that IL-15 gene silencing alone and combination in NiMOS significantly reduced other proinflammatory cytokines. The tissue histopathology data also confirmed a reduction in immune cell infiltration as well as restoration of the mucosal architecture and barrier function in the intestine upon treatment. Overall, the results of this study show evidence that celiac disease can be potentially treated with an oral microsphere formulation using a combination of TG2 and IL-15 RNA interference therapeutic strategy.

RNA Interference-Mediated Gene Silencing of Pleiotrophin Through Polyethylenimine-Complexed Small Interfering RNAs In Vivo Exerts Antitumoral Effects in Glioblastoma Xenografts

2006 ◽  
Vol 0 (0) ◽  
pp. 060801084750001
Author(s):  
Marius Grzelinski ◽  
Beata Urban-Klein ◽  
Tobias Martens ◽  
Katrin Lamszus ◽  
Udo Bakowsky ◽  
...  
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Small Interfering Rnas

scholarly journals Effect of Adenovirus-Mediated RNA Interference on Endogenous MicroRNAs in a Mouse Model of Multidrug Resistance Protein 2 Gene Silencing

2006 ◽  
Vol 80 (24) ◽  
pp. 12236-12247 ◽  
Author(s):  
Iñigo Narvaiza ◽  
Oscar Aparicio ◽  
María Vera ◽  
Nerea Razquin ◽  
Sergia Bortolanza ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Rna Interference ◽  
Gene Silencing ◽  
Viral Vectors ◽  
Minimal Amount ◽  
Multidrug Resistance Protein ◽  
Shrna Expression ◽  
Multidrug Resistance Protein 2 ◽  
Resistance Protein

ABSTRACT RNA interference with viral vectors that express short hairpin RNAs (shRNAs) has emerged as a powerful tool for functional genomics and therapeutic purposes. However, little is known about shRNA in vivo processing, accumulation, functional kinetics, and side effects related to shRNA saturation of the cellular gene silencing machinery. Therefore, we constructed first-generation recombinant adenoviruses encoding different shRNAs against murine ATP-binding cassette multidrug resistance protein 2 (Abcc2), which is involved in liver transport of bilirubin to bile, and analyzed Abcc2 silencing kinetics. C57/BL6 mice injected with these viruses showed significant impairment of Abcc2 function for up to 3 weeks, as reflected by increased serum bilirubin levels. The lack of Abcc2 function correlated with a specific reduction of Abcc2 mRNA and with high levels of processed shRNAs targeting Abcc2. Inhibition was lost at longer times postinfection, correlating with a decrease in the accumulation of processed shRNAs. This finding suggests that a minimal amount of processed shRNAs is required for efficient silencing in vivo. This system was also used to evaluate the effect of shRNA expression on the saturation of silencing factors. Saturation of the cellular silencing processing machinery alters the accumulation and functionality of endogenous microRNAs (miRNAs) and pre-miRNAs. However, expression of functional exogenous shRNAs did not change the levels of endogenous miRNAs or their precursors. In summary, this work shows that adenoviral vectors can deliver sufficient shRNAs to mediate inhibition of gene expression without saturating the silencing machinery.

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