Functional delivery of DNAzyme with iron oxide nanoparticles for hepatitis C virus gene knockdown

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DNAzyme is an attractive therapeutic oligonucleotide which enables cleavage of mRNA in a sequence-specific manner and thus, silencing target gene. A particularly important challenge in achieving the successful down-regulation of gene expression is to efficiently deliver DNAzymes to disease sites and cells. Here, we report the nanoparticle-assisted functional delivery of therapeutic DNAzyme for the treatment of hepatitis C by inducing knockdown of hepatitis C virus (HCV) gene, NS3. HCV NS3 gene encodes helicase and protease which are essential for the virus replication. The nanocomplex showed efficient NS3 knockdown while not evoking undesired immune responses or notable cytotoxicity. We also demonstrated the DNAzyme conjugated nanoparticle system could be applicable in vivo by showing the accumulation of the nanoparticles in liver, and more specifically, in hepatocytes. We believe that the present work is a successful demonstration of effective, functional, non-immunostimulatory DNAzyme delivery system based on inorganic nanoparticles with high potential for further therapeutic application of DNAzyme in the treatment of hepatitis C. (C) 2011 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2012-03
Language
English
Article Type
Article
Keywords

CLEAVING DNA ENZYME; IMMUNE ACTIVATION; INTERFERON-ALPHA; RNA HELICASE; TAT PEPTIDE; IN-VITRO; THERAPY; REPLICATION; RIBAVIRIN; MODEL

Citation

BIOMATERIALS, v.33, no.9, pp.2754 - 2761

ISSN
0142-9612
DOI
10.1016/j.biomaterials.2011.12.015
URI
http://hdl.handle.net/10203/98164
Appears in Collection
CH-Journal Papers(저널논문)
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