Gene manipulation through the use of small interfering RNA (siRNA): From in vitro to in vivo applications

Kumar, Lekha Dinesh; Clarke, Alan R.

doi:10.1016/j.addr.2007.03.009

Cited by 67 publications

(36 citation statements)

References 171 publications

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“…15 According to previous report, 16 siRNA, which is 21-bp long with two 3 0 -overhangs can silence mammal gene effectively and specifically. The chemical synthesis of siRNA in vitro is the oldest and most traditional way of synthesis, which has the advantage of easy preparation, high purity and low toxicity, easy labeling, and tracking in vivo.…”

Section: Discussionmentioning

confidence: 96%

Inhibition ofPAX2Gene Expression by siRNA (Polyethylenimine) in Experimental Model of Obstructive Nephropathy

Wang

et al. 2012

Renal Failure

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Objective: It was found that PAX2 (Paired Box 2) re-expression in renal tubular epithelial cells correlated with renal interstitial fibrosis of rats with obstructive nephropathy. The purpose of the present study was to identify whether RNA interference (RNAi) induced by polyethylenimine (jetPEI) could inhibit PAX2 gene re-expression and impact renal interstitial fibrosis of rats with obstructive nephropathy. Methods: Four pairs of small interfering RNA (siRNA) interference sequences and a negative control were designed and synthesized according to the whole PAX2 gene mRNA sequence. siRNA was then transfected into renal capsule in a rodent model of unilateral ureteral obstruction (UUO), using in vivo jetPEI as delivery vector. The expression of PAX2 mRNA and protein in renal tissue was determined by real-time quantitative polymerase chain reaction (PCR) and Western blot, respectively. A carboxyfluorescein (FAM)-labeled negative control was also synthesized at the same time to identify transfection in vivo. Renal interstitial fibrosis was observed under light microscope after PAX2 gene silenced. Results: Green fluorescence was observed around renal tubule epithelial cells by fluorescence microscopy 3 days after the procedure validating the success of transfection. While the PAX2 gene expression was inhibited by all siRNA interference sequences, the strongest inhibition was observed with siRNA3. The PAX2 mRNA and protein were inhibited by 55% and 81%, respectively. Renal tubular damage and renal interstitial fibrosis were remitted obviously after PAX2 gene silenced. Conclusion: siRNA was able to inhibit the expression of PAX2 in tubular epithelial cells in the UUO model. The siRNA may thus provide therapeutic potential for retarding the pathological progression of UUO.

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Section: Discussionmentioning

confidence: 96%

Inhibition ofPAX2Gene Expression by siRNA (Polyethylenimine) in Experimental Model of Obstructive Nephropathy

Wang

et al. 2012

Renal Failure

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“…Therefore, retroviruses and lentiviruses can be used to attain a stable gene knockdown while adenoviruses are more suitable to attain transient gene silencing. Lentiviral and adenoviral vectors work in both dividing and non-dividing cells, and consequently can be used to infect terminally differentiated cells such as neurons, muscle and liver cells; in contrast, retroviruses only infect replicative cells and hence can be reliably used in cancer therapy in vivo (44). Having been used in several preclinical and clinical trials, viral vectors with specific properties provide various choices and flexibility in targeting inherited and acquired diseases with antisense strategies.…”

Section: Delivery Systemsmentioning

confidence: 99%

Antisense Makes Sense in Engineered Regenerative Medicine

et al. 2008

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The use of antisense strategies such as ribozymes, oligodeoxynucleotides (ODNs) and small interfering RNA (siRNA) in gene therapy, in conjunction with the use of stem cells and tissue engineering, has opened up possibilities in curing degenerative diseases and injuries to non-regenerating organs and tissues. With their unique ability to down-regulate or silence gene expression, antisense oligonucleotides are uniquely suited in turning down the production of pathogenic or undesirable proteins and cytokines. Here, we review the antisense strategies and their applications in regenerative medicine with a focus on their efficacies in promoting cell viability, regulating cell functionalities as well as shaping an optimal microenvironment for therapeutic purposes.

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“…One such approach is the use of RNA interference (RNAi) technology. Recent breakthroughs in RNAi technology have vastly improved our understanding of how gene expression can be specifically modulated and can be employed as a potential therapeutic tool (4)(5)(6)(7). Harnessing small RNA molecules to silence genes involved in the development and growth of cancer cells is an important step forward in developing a new and targetfocused cancer therapy (8).…”

Section: Introductionmentioning

confidence: 99%

RNA Interference Using c-Myc–Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models

Tangudu

Verma

Clemons

et al. 2015

Molecular Cancer Therapeutics

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In this article, we report the development and preclinical validation of combinatorial therapy for treatment of cancers using RNA interference (RNAi). RNAi technology is an attractive approach to silence genes responsible for disease onset and progression. Currently, the critical challenge facing the clinical success of RNAi technology is in the difficulty of delivery of RNAi inducers, due to low transfection efficiency, difficulties of integration into host DNA and unstable expression. Using the macromolecule polyglycidal methacrylate (PGMA) as a platform to graft multiple polyethyleneimine (PEI) chains, we demonstrate effective delivery of small oligos (anti-miRs and mimics) and larger DNAs (encoding shRNAs) in a wide variety of cancer cell lines by successful silencing/activation of their respective target genes. Furthermore, the effectiveness of this therapy was validated for in vivo tumor suppression using two transgenic mouse models; first, tumor growth arrest and increased animal survival was seen in mice bearing Brca2/p53-mutant mammary tumors following daily intratumoral treatment with nanoparticles conjugated to c-Myc shRNA. Second, oral delivery of the conjugate to an Apc-deficient crypt progenitor colon cancer model increased animal survival and returned intestinal tissue to a non-wnt-deregulated state. This study demonstrates, through careful design of nonviral nanoparticles and appropriate selection of therapeutic gene targets, that RNAi technology can be made an affordable and amenable therapy for cancer. Mol Cancer Ther; 14(5); 1259-69. Ó2015 AACR.

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Gene manipulation through the use of small interfering RNA (siRNA): From in vitro to in vivo applications

Cited by 67 publications

References 171 publications

Inhibition ofPAX2Gene Expression by siRNA (Polyethylenimine) in Experimental Model of Obstructive Nephropathy

Inhibition ofPAX2Gene Expression by siRNA (Polyethylenimine) in Experimental Model of Obstructive Nephropathy

Antisense Makes Sense in Engineered Regenerative Medicine

RNA Interference Using c-Myc–Conjugated Nanoparticles Suppresses Breast and Colorectal Cancer Models

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