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Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression

(2012) PHARMACEUTICAL RESEARCH. 29(3). p.669-682
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Abstract
Tumor necrosis factor alpha (TNF-alpha) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-alpha expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-alpha siRNA with optimal efficacy and minimal off-target effects in vitro. TNF-alpha silencing with polymeric siRNA nanocarriers was compared in lipopolysaccharide-activated RAW 264.7 macrophages by real-time reverse transcription (RT)-PCR. Expression of non-target genes involved in inflammation, apoptosis, and cell cycle progression was determined by RT-PCR, toxicity evaluated by propidium iodide and annexin V staining. PAMAM dendrimers (G4 and G7) and dextran nanogels mediated remarkably high concentration-dependent gene silencing and low toxicity; dioleoyltrimethylammoniumpropane-modified poly(DL-lactide-co-glycolide acid) nanoparticles, thiolated, trimethylated chitosan and poly[(2-hydroxypropyl)methacrylamide 1-methyl-2-piperidine methanol] polyplexes were less efficient transfectants. There were minor changes in the regulation of off-target genes, mainly dependent on nanocarrier and siRNA concentration. Dextran nanogels and PAMAM dendrimers mediated high gene silencing with minor toxicity and off-target transcriptional changes and are therefore expected to be suitable siRNA delivery systems in vivo.
Keywords
NECROSIS-FACTOR-ALPHA, RHEUMATOID-ARTHRITIS, EPITHELIAL A549 CELLS, DRUG-DELIVERY SYSTEMS, COLLAGEN-INDUCED ARTHRITIS, BIODEGRADABLE DEXTRAN NANOGELS, SMALL INTERFERING RNA, TNF-alpha, siRNA, polymer, delivery, macrophages, IN-VIVO, DNA COMPLEXES, CANCER-CELLS

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Citation

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MLA
Jensen, Linda B., et al. “Comparison of Polymeric SiRNA Nanocarriers in a Murine LPS-Activated Macrophage Cell Line: Gene Silencing, Toxicity and off-Target Gene Expression.” PHARMACEUTICAL RESEARCH, vol. 29, no. 3, 2012, pp. 669–82, doi:10.1007/s11095-011-0589-0.
APA
Jensen, L. B., Griger, J., Naeye, B., Varkouhi, A. K., Raemdonck, K., Schiffelers, R., … Foged, C. (2012). Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression. PHARMACEUTICAL RESEARCH, 29(3), 669–682. https://doi.org/10.1007/s11095-011-0589-0
Chicago author-date
Jensen, Linda B, Joscha Griger, Broes Naeye, Amir K Varkouhi, Koen Raemdonck, Raymond Schiffelers, Twan Lammers, et al. 2012. “Comparison of Polymeric SiRNA Nanocarriers in a Murine LPS-Activated Macrophage Cell Line: Gene Silencing, Toxicity and off-Target Gene Expression.” PHARMACEUTICAL RESEARCH 29 (3): 669–82. https://doi.org/10.1007/s11095-011-0589-0.
Chicago author-date (all authors)
Jensen, Linda B, Joscha Griger, Broes Naeye, Amir K Varkouhi, Koen Raemdonck, Raymond Schiffelers, Twan Lammers, Gert Storm, Stefaan De Smedt, Brian S Sproat, Hanne M Nielsen, and Camilla Foged. 2012. “Comparison of Polymeric SiRNA Nanocarriers in a Murine LPS-Activated Macrophage Cell Line: Gene Silencing, Toxicity and off-Target Gene Expression.” PHARMACEUTICAL RESEARCH 29 (3): 669–682. doi:10.1007/s11095-011-0589-0.
Vancouver
1.
Jensen LB, Griger J, Naeye B, Varkouhi AK, Raemdonck K, Schiffelers R, et al. Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression. PHARMACEUTICAL RESEARCH. 2012;29(3):669–82.
IEEE
[1]
L. B. Jensen et al., “Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression,” PHARMACEUTICAL RESEARCH, vol. 29, no. 3, pp. 669–682, 2012.
@article{2137021,
  abstract     = {{Tumor necrosis factor alpha (TNF-alpha) plays a key role in the progression of rheumatoid arthritis and is an important target for anti-rheumatic therapies. TNF-alpha expression can be silenced with small interfering RNA (siRNA), but efficacy is dependent on efficient and safe siRNA delivery vehicles. We aimed to identify polymeric nanocarriers for anti-TNF-alpha siRNA with optimal efficacy and minimal off-target effects in vitro. 
TNF-alpha silencing with polymeric siRNA nanocarriers was compared in lipopolysaccharide-activated RAW 264.7 macrophages by real-time reverse transcription (RT)-PCR. Expression of non-target genes involved in inflammation, apoptosis, and cell cycle progression was determined by RT-PCR, toxicity evaluated by propidium iodide and annexin V staining. 
PAMAM dendrimers (G4 and G7) and dextran nanogels mediated remarkably high concentration-dependent gene silencing and low toxicity; dioleoyltrimethylammoniumpropane-modified poly(DL-lactide-co-glycolide acid) nanoparticles, thiolated, trimethylated chitosan and poly[(2-hydroxypropyl)methacrylamide 1-methyl-2-piperidine methanol] polyplexes were less efficient transfectants. There were minor changes in the regulation of off-target genes, mainly dependent on nanocarrier and siRNA concentration. 
Dextran nanogels and PAMAM dendrimers mediated high gene silencing with minor toxicity and off-target transcriptional changes and are therefore expected to be suitable siRNA delivery systems in vivo.}},
  author       = {{Jensen, Linda B and Griger, Joscha and Naeye, Broes and Varkouhi, Amir K and Raemdonck, Koen and Schiffelers, Raymond and Lammers, Twan and Storm, Gert and De Smedt, Stefaan and Sproat, Brian S and Nielsen, Hanne M and Foged, Camilla}},
  issn         = {{0724-8741}},
  journal      = {{PHARMACEUTICAL RESEARCH}},
  keywords     = {{NECROSIS-FACTOR-ALPHA,RHEUMATOID-ARTHRITIS,EPITHELIAL A549 CELLS,DRUG-DELIVERY SYSTEMS,COLLAGEN-INDUCED ARTHRITIS,BIODEGRADABLE DEXTRAN NANOGELS,SMALL INTERFERING RNA,TNF-alpha,siRNA,polymer,delivery,macrophages,IN-VIVO,DNA COMPLEXES,CANCER-CELLS}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{669--682}},
  title        = {{Comparison of polymeric siRNA nanocarriers in a murine LPS-activated macrophage cell line: gene silencing, toxicity and off-target gene expression}},
  url          = {{http://doi.org/10.1007/s11095-011-0589-0}},
  volume       = {{29}},
  year         = {{2012}},
}

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