Functional delivery of DNAzyme with iron oxide nanoparticles for hepatitis C virus gene knockdown.
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.
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
Soo-Ryoon
SR
Ryoo
Hongje
H
Jang
Ki-Sun
KS
Kim
Bokhui
B
Lee
Kyung Bo
KB
Kim
Young-Kwan
YK
Kim
Woon-Seok
WS
Yeo
Younghoon
Y
Lee
Dong-Eun
DE
Kim
Dal-Hee
DH
Min
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D021881:DNA, Catalytic / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry*; D055785:Gene Knockdown Techniques / Q000379:methods*; D018014:Gene Transfer Techniques; D016174:Hepacivirus / Q000235:genetics*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012093:Replicon / Q000235:genetics; D014018:Tissue Distribution; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D021881:DNA, Catalytic; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C000499:ferric oxide