Inhibition of hepatitis C virus in mouse models by lipidoid nanoparticle-mediated systemic delivery of siRNA against PRK2
- 주제(키워드) Antivirals , HCV , Lipidoid , Nanoparticles , PRK2 , SiRNA
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier Inc.
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000131051
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.nano.2016.02.015
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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. © 2016 Elsevier Inc.
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