Targeted delivery of anti-coxsackievirus siRNAs using ligand-conjugated packaging RNAs

Huifang M. Zhang, Yue Su, Songchuan Guo, Ji Yuan, Travis Lim, Jing Liu, Peixuan Guo, Decheng Yang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Coxsackievirus B3 (CVB3) is a common pathogen of myocarditis. We previously synthesized a siRNA targeting the CVB3 protease 2A (siRNA/2A) gene and achieved reduction of CVB3 replication by 92% in vitro. However, like other drugs under development, CVB3 siRNA faces a major challenge of targeted delivery. In this study, we investigated a novel approach to deliver CVB3 siRNAs to a specific cell population (e.g. HeLa cells containing folate receptor) using receptor ligand (folate)-linked packaging RNA (pRNA) from bacterial phage phi29. pRNA monomers can spontaneously form dimers and multimers under optimal conditions by base-pairing between their stem loops. By covalently linking a fluorescence-tag to folate, we delivered the conjugate specifically to HeLa cells without the need of transfection. We further demonstrated that pRNA covalently conjugated to siRNA/2A achieved an equivalent antiviral effect to that of the siRNA/2A alone. Finally, the drug targeted delivery was further evaluated by using pRNA monomers or dimers, which carried both the siRNA/2A and folate ligand and demonstrated that both of them strongly inhibited CVB3 replication. These data indicate that pRNA as a siRNA carrier can specifically deliver the drug to target cells via its ligand and specific receptor interaction and inhibit virus replication effectively.

Original languageEnglish (US)
Pages (from-to)307-316
Number of pages10
JournalAntiviral Research
Volume83
Issue number3
DOIs
StatePublished - Sep 1 2009

Fingerprint

Enterovirus
Product Packaging
Small Interfering RNA
RNA
Ligands
Folic Acid
HeLa Cells
RNA Phages
Pharmaceutical Preparations
Myocarditis
Virus Replication
Base Pairing
Antiviral Agents
Transfection
Fluorescence
Population
Genes

Keywords

  • Coxsackievirus B3
  • Drug delivery
  • Folate receptor
  • Gene therapy
  • Packaging RNA
  • siRNA

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Targeted delivery of anti-coxsackievirus siRNAs using ligand-conjugated packaging RNAs. / Zhang, Huifang M.; Su, Yue; Guo, Songchuan; Yuan, Ji; Lim, Travis; Liu, Jing; Guo, Peixuan; Yang, Decheng.

In: Antiviral Research, Vol. 83, No. 3, 01.09.2009, p. 307-316.

Research output: Contribution to journalArticle

Zhang, Huifang M. ; Su, Yue ; Guo, Songchuan ; Yuan, Ji ; Lim, Travis ; Liu, Jing ; Guo, Peixuan ; Yang, Decheng. / Targeted delivery of anti-coxsackievirus siRNAs using ligand-conjugated packaging RNAs. In: Antiviral Research. 2009 ; Vol. 83, No. 3. pp. 307-316.
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