ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
A DNA microarray-based analysis of the host response to a nonviral gene carrier: a strategy for improving the immune response.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 20 citations in OpenAlex.
- Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model.Nature materials · 2016Article
- Activation of TLR9 by incorporated pDNA within PEG-coated lipoplex enhances anti-PEG IgM production.Gene therapy · 2014Article
- Clinical significance of metallothioneins in cell therapy and nanomedicine.International journal of nanomedicine · 2013Review
- Designing an organellar postal service: delivery of macromolecules to mitochondria in intact cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
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9 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The purpose of this study was to investigate the host response to systemically administered lipid nanoparticles (NPs) encapsulating plasmid DNA (pDNA) in the spleen using a DNA microarray. As a model for NPs, we used a multifunctional envelope-type nano device (MEND). Microarray analysis revealed that 1,581 of the differentially expressed genes could be identified by polyethylene glycol (PEG)-unmodified NP using a threefold change relative to the control. As the result of PEGylation, the NP treatment resulted in the reduction in the expression of most of the genes. However, the expression of type I interferon (IFN) was specifically increased by PEGylation. Based on the microarray and a pathway analysis, we hypothesize that PEGylation inhibited the endosomal escape of NP, and extended the interaction of toll-like receptor-9 (TLR9) with CpG-DNA accompanied by the production of type I IFN. This hypothesis was tested by introducing a pH-sensitive fusogenic peptide, GALA, which enhances the endosomal escape of PEGylated NP. As expected, type I IFN was reduced and interleukin-6 (IL-6) remained at the baseline. These findings indicate that a carrier design based on microarray analysis and the manipulation of intracellular trafficking constitutes a rational strategy for reducing the host immune response to NPs.
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Registered trials
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