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

Jae Su Moon, Seung Hoon Lee, Song Hee Han, Eun Jung Kim, Hee Cho, Wooseong Lee, Mi Kyung Kim, Tae Eun Kim, Hyun Ji Park, Jin Kyu Rhee, Seong Jun Kim, Seung-Woo Cho, Seung Hyun Han, Jong-Won Oh

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 log10 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.

Original languageEnglish
Pages (from-to)1489-1498
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number6
DOIs
Publication statusPublished - 2016 Aug 1

Fingerprint

Viruses
Hepacivirus
Nanoparticles
Protein Kinase C
Small Interfering RNA
Phosphotransferases
Proteins
Virus Replication
RNA
Antiviral Agents
RNA Replicase
protein kinase C kinase
Viral Load
Heterografts
Genes
Genome
Injections
Therapeutics
Serum

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Moon, Jae Su ; Lee, Seung Hoon ; Han, Song Hee ; Kim, Eun Jung ; Cho, Hee ; Lee, Wooseong ; Kim, Mi Kyung ; Kim, Tae Eun ; Park, Hyun Ji ; Rhee, Jin Kyu ; Kim, Seong Jun ; Cho, Seung-Woo ; Han, Seung Hyun ; Oh, Jong-Won. / Inhibition of hepatitis C virus in mouse models by lipidoid nanoparticle-mediated systemic delivery of siRNA against PRK2. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2016 ; Vol. 12, No. 6. pp. 1489-1498.
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Inhibition of hepatitis C virus in mouse models by lipidoid nanoparticle-mediated systemic delivery of siRNA against PRK2. / Moon, Jae Su; Lee, Seung Hoon; Han, Song Hee; Kim, Eun Jung; Cho, Hee; Lee, Wooseong; Kim, Mi Kyung; Kim, Tae Eun; Park, Hyun Ji; Rhee, Jin Kyu; Kim, Seong Jun; Cho, Seung-Woo; Han, Seung Hyun; Oh, Jong-Won.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 12, No. 6, 01.08.2016, p. 1489-1498.

Research output: Contribution to journalArticle

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