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 journalArticlepeer-review

12 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

Bibliographical note

Funding Information:
Funding: This work was supported by a grant from the Technology Innovation Program (MKE 10035159) funded by the Ministry of Knowledge Economy (MKE, Korea) and in part by grants from the National Research Foundation of Korea funded by the Korea government (MSIP) (NRF 2009–0083522, 2010–0025982, 2013–063182, 2014R1A2A2A01005522, and COMPA 2014-11-1672).

Publisher Copyright:
© 2016 Elsevier Inc.

All Science Journal Classification (ASJC) codes

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

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