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

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.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Zhang HM,Su Y,Guo S,Yuan J,Lim T,Liu J,Guo P,Yang D

doi

10.1016/j.antiviral.2009.07.005

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

307-16

issue

3

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(09)00383-0

journal_volume

83

pub_type

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