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 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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