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Suppressive effects of sugar-modified cationic liposome/NF-κB decoy complexes on adenovirus vector-induced innate immune responses
- Source :
-
Journal of Controlled Release . Jan2009, Vol. 133 Issue 2, p139-145. 7p. - Publication Year :
- 2009
-
Abstract
- Abstract: To date, no countermeasures have been developed to overcome adenovirus (Ad) vector-induced innate immune responses in gene therapies that utilize these vectors. In the present study, we attempted to suppress Ad vector-induced innate immune responses and hepatotoxicity by delivering an NF-κB decoy to splenic macrophages and dendritic cells, as well as to Kupffer cells in the liver, using sugar-modified cationic liposomes. Pre-injection of the sugar-modified cationic liposome/NF-κB decoy complexes reduced serum levels of interleukin (IL)-12, which is a typical inflammatory cytokine induced by Ad vectors, and also reduced hepatotoxicity following Ad vector injection. Electrophoretic mobility shift assay demonstrated a reduction of Ad vector-induced NF-κB activation by pre-injection of the sugar-modified cationic liposome/NF-κB decoy complexes. Two types of sugar-modified cationic liposomes, fucosylated cationic liposomes (Fuc-liposomes) and mannosylated cationic liposomes (Man-liposomes), were tested in this study. Man-liposomes, which are considered to have greater affinity than Fuc-liposomes for splenocytes, appeared to have superior suppressive effects to those of Fuc-liposomes. Pre-injection of the sugar-modified cationic liposome/NF-κB decoy complexes did not inhibit Ad vector-mediated transduction in the organs. This study provides important findings for overcoming Ad vector-induced innate immune responses. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 133
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 35768233
- Full Text :
- https://doi.org/10.1016/j.jconrel.2008.09.081