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

E. Y. Kim; R. Schulz; P. Swantek; K. Kunstman; M. H. Malim; S. M. Wolinsky

doi:10.1038/gt.2011.95

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

E. Y. Kim, R. Schulz, P. Swantek, K. Kunstman, M. H. Malim, S. M. Wolinsky^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

52 Scopus citations

Abstract

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 nanoparticle conjugates in translational research and in the development of therapeutics and gene delivery systems.

Original language	English (US)
Pages (from-to)	347-353
Number of pages	7
Journal	Gene therapy
Volume	19
Issue number	3
DOIs	https://doi.org/10.1038/gt.2011.95
State	Published - Mar 2012

Funding

The National Institutes of Health, the National Science Foundation, the United Kingdom Medical Research Council and the International Institute for Nanotechnology within Northwestern University supported this study. Data were presented at the 2009 meeting of the International Institute for Nanotechnology, Nanoscale Science and Engineering Center for Integrated Nanopatterning and Detection Technologies, Northwestern University. EK is the recipient of a Baxter Award from the Institute for BioNanotechnology in Medicine. RS is a Research Councils UK Academic Fellow. All patient samples were collected with Northwestern University Institutional Review Board (IRB) consent. We thank David Giljohann and Chad Mirkin for generously providing the gold nanoparticles stably functionalized with covalently attached oligonucleotides; Edward Campbell and Kelly Fahrbach for assistance with fluorescent microscopy; Robert Goldman and Lennell Raynolds for assistance with transmission electron microscopy; Carlos Nahas and Maurice O’Gorman for assistance with FACS analysis; and Jaejung Kim for assistance with the human microarrays. The microarray data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (www.ncbi.nlm.nih. gov/geo) and are accessible through GSE 20677 Series accession numbers GSM518597 to GSM518609 and GSM535541 to GSM535543.

Keywords

gene delivery
gene expression
gold nanoparticle-oligonucleotide complexes
immune activation
signaling pathways

ASJC Scopus subject areas

Genetics
Molecular Medicine
Molecular Biology

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abstract = "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 nanoparticle conjugates in translational research and in the development of therapeutics and gene delivery systems.",

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

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