Galactosylated Lipidoid Nanoparticles for Delivery of Small Interfering RNA to Inhibit Hepatitis C Viral Replication In Vivo

Hyun Ji Park, Eun Je Jeon, Jung Seung Lee, Sang Hyeon Hong, Ann Na Cho, Joan Lee, Jae Su Moon, Kyeong Eun Jung, Jong-Won Oh, Haeshin Lee, Seung-Woo Cho

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Small interfering RNA (siRNA) delivery can provide an effective therapy for treating viral diseases by silencing genes involved in viral replication. In this study, a liver-targeting formulation of lipidoid nanoparticle for delivery of siRNA that targets protein kinase C-related kinase 2 (PRK2) to inhibit hepatitis C virus (HCV) replication is reported. The most effective, minimally cytotoxic lipidoid for siRNA delivery to hepatic cells is identified from a small library of alkyl epoxide–polyamine conjugates. In vitro transfection of PRK2 siRNA (siPRK2) using this lipidoid induces significant silencing of PRK2 (≈80%), suppressing HCV replication in human hepatic cells transfected with the HCV subgenomic replicon. Systemic administration of siPRK2 using the lipidoid nanoparticles results in significant reduction of host PRK2 in the mouse liver (≈60%). This treatment significantly suppresses HCV replication in an HCV-xenograft mouse model. siRNA delivery to the liver is further improved via galactosylation of the lipidoid. Compared with the unmodified lipidoid formulation, galactosylated lipidoids induce greater silencing of host PRK2 in mouse livers (≈80%) and more rapid suppression of HCV replication in an HCV-xenograft mouse. This study suggests that galactosylated lipidoid nanoparticles could provide a treatment for hepatitis C by mediating delivery of anti-viral RNA interference therapeutics to the liver.

Original languageEnglish
Pages (from-to)2931-2941
Number of pages11
JournalAdvanced healthcare materials
Volume5
Issue number22
DOIs
Publication statusPublished - 2016 Nov 23

Fingerprint

Hepatitis C
RNA
Viruses
Hepacivirus
Nanoparticles
Small Interfering RNA
Liver
Protein Kinase C
Virus Replication
Phosphotransferases
Proteins
Heterografts
Hepatocytes
Viral Interference
Replicon
Viral RNA
Gene Silencing
Virus Diseases
RNA Interference
Libraries

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

Park, Hyun Ji ; Jeon, Eun Je ; Lee, Jung Seung ; Hong, Sang Hyeon ; Cho, Ann Na ; Lee, Joan ; Moon, Jae Su ; Jung, Kyeong Eun ; Oh, Jong-Won ; Lee, Haeshin ; Cho, Seung-Woo. / Galactosylated Lipidoid Nanoparticles for Delivery of Small Interfering RNA to Inhibit Hepatitis C Viral Replication In Vivo. In: Advanced healthcare materials. 2016 ; Vol. 5, No. 22. pp. 2931-2941.
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Galactosylated Lipidoid Nanoparticles for Delivery of Small Interfering RNA to Inhibit Hepatitis C Viral Replication In Vivo. / Park, Hyun Ji; Jeon, Eun Je; Lee, Jung Seung; Hong, Sang Hyeon; Cho, Ann Na; Lee, Joan; Moon, Jae Su; Jung, Kyeong Eun; Oh, Jong-Won; Lee, Haeshin; Cho, Seung-Woo.

In: Advanced healthcare materials, Vol. 5, No. 22, 23.11.2016, p. 2931-2941.

Research output: Contribution to journalArticle

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