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Inhibition of hepatitis C virus in mouse models by lipidoid nanoparticle-mediated systemic delivery of siRNA against PRK2

Title
Inhibition of hepatitis C virus in mouse models by lipidoid nanoparticle-mediated systemic delivery of siRNA against PRK2
Authors
Moon, Jae-SuLee, Seung-HoonHan, Song-HeeKim, Eun-JungCho, HeeLee, WooseongKim, Mi-KyungKim, Tae-EunPark, Hyun-JiRhee, Jin-KyuKim, Seong-JunCho, Seung-WooHan, Seung HyunOh, Jong-Won
Ewha Authors
이진규
SCOPUS Author ID
이진규scopus
Issue Date
2016
Journal Title
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
ISSN
1549-9634JCR Link

1549-9642JCR Link
Citation
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE vol. 12, no. 6, pp. 1489 - 1498
Keywords
HCVsiRNALipidoidNanoparticlesPRK2Antivirals
Publisher
ELSEVIER SCIENCE BV
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Host-targeting antivirals have an advantage over direct-acting antivirals in that they have a high genetic barrier to resistance. Here, we describe in vivo anti-hepatitis C virus (HCV) efficacy of a potent siRNA targeting the protein kinase C-related kinase 2 (PRK2), which phosphorylates HCV NS5B RNA-dependent RNA polymerase and promotes HCV replication. PRK2-silencing reduced the phosphorylated NS5B level and resulted in inhibition of NS5B RdRp activity to decrease HCV genome abundance. Systemic administration of lipidoid nanoparticle-formulated PRK2 siRNA (once every three days for a total of three injections at a dose of 3 mg kg(-1)) resulted in a 3.72 and 1.96 log(10) reduction in serum HCV RNA titer, in mouse subcutaneous and orthotopic xenograft models for HCV replication, respectively. Our results verify the essential role of PRK2 in HCV replication and offer a host-targeting anti-HCV siRNA therapy that might be beneficial for non-responders to current treatment regimens. (C) 2016 Elsevier Inc. All rights reserved.
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DOI
10.1016/j.nano.2016.02.015
Appears in Collections:
엘텍공과대학 > 식품공학전공 > Journal papers
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