Unknown,Transcriptomics,Genomics,Proteomics

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Gene Expression in Gold Nanoparticle Oligonucleotide Complexes treated Primary Immune Cells


ABSTRACT: Gold nanoparticle (Au—NP) oligonucleotide complexes hold considerable promise as an approach for manipulating intracellular gene regulation. We show that the uptake and intracellular fate of Au—NP oligonucleotide complexes is associated with endocytosis and signal transduction. A transcriptome—wide functional analysis of gene expression implicated multiple signaling pathways specific for Au—NP oligonucleotide complexes. In primary immune cells, the complexes trigger the expression of pro—inflammatory non—chemotactic cytokines rather than the many IFN—stimulated genes critical for induction of the immune response to a microbial challenge. Concordant with these changes, exposure to Au—NP oligonucleotide complexes is also accompanied by marked activation of immune cells. This distinct gene expression profile is not replicated in the lineage—restricted 293T cell line. These findings provide insight into the functional significance of the recruitment of Au—NP oligonucleotide complexes to endocytic structures and highlight the need to study the systems effects of nanomaterials in a biologically relevant model. We investigated the effect of Au—NP antisense EGFP oligonucleotide complexes on the transcriptome by expression profiling of 293T cells under four conditions and PBMCs under six conditions plus HIV infection with the Affymetrix U133 Plus 2.0 microarray. To control for experimental variability, three of the six PBMC conditions (24— and 48—hours after Au—NP oligonucleotide complex treatment, and the negative control) were assayed independently a second time (biological replicates) so that 13 microarrays were hybridized in total. A different batch of Au—NP oligonucleotide complexes was used in the generation of the four 293T and three replicate PBMC samples, and the microarrays for these samples were processed separately.

ORGANISM(S): Homo sapiens

SUBMITTER: Eunyoung Kim 

PROVIDER: E-GEOD-20677 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gold nanoparticle-mediated gene delivery induces widespread changes in the expression of innate immunity genes.

Kim E-Y EY   Schulz R R   Swantek P P   Kunstman K K   Malim M H MH   Wolinsky S M SM  

Gene therapy 20110623 3


The unique properties of oligonucleotide (and small interfering RNA)-modified gold nanoparticle conjugates make them promising intracellular gene regulation agents. We found that gold nanoparticles stably functionalized with covalently attached oligonucleotides activate immune-related genes and pathways in human peripheral blood mononuclear cells, but not an immortalized, lineage-restricted cell line. These findings have strong implications for the application of oligonucleotide-modified gold na  ...[more]

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