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

Abstract 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...

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Bibliographic Details
Published in:Biomaterials 2012-03, Vol.33 (9), p.2754-2761
Main Authors: Ryoo, Soo-Ryoon, Jang, Hongje, Kim, Ki-Sun, Lee, Bokhui, Kim, Kyung Bo, Kim, Young-Kwan, Yeo, Woon-Seok, Lee, Younghoon, Kim, Dong-Eun, Min, Dal-Hee
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Base Sequence
Cell Line, Tumor
Dentistry
DNA, Catalytic - metabolism
DNAzyme
Drug delivery
Ferric Compounds - chemistry
Gene Knockdown Techniques - methods
Gene Transfer Techniques
Hepacivirus - genetics
Hepatocytes - virology
Humans
Magnetic nanoparticle
Magnetite Nanoparticles - chemistry
Magnetite Nanoparticles - ultrastructure
Mice
Mice, Inbred C57BL
Mice, Nude
Molecular Sequence Data
Replicon - genetics
Tissue Distribution
Viral Nonstructural Proteins - genetics
Virus
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Summary:Abstract 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2011.12.015