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Targeted Small Interfering RNA- Immunoliposomes as a Promising Therapeutic Agent against Highly Pathogenic Avian Influenza A (H5N1) Virus Infection
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Document Title
Targeted Small Interfering RNA- Immunoliposomes as a Promising Therapeutic Agent against Highly Pathogenic Avian Influenza A (H5N1) Virus Infection
Author
Khantasup K, Kopermsu P, Chaichoun K, Dharakul T
Name from Authors Collection
Affiliations
Mahidol University; National Science & Technology Development Agency - Thailand; National Nanotechnology Center (NANOTEC); Mahidol University
Type
Article
Source Title
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN
0066-4804
Year
2014
Volume
58
Issue
1
Open Access
Green Published
Publisher
AMER SOC MICROBIOLOGY
DOI
10.1128/AAC.02768-13
Format
Abstract
This study describes a proof- of- concept study on the use of small interfering RNA (siRNA)- immunoliposomes as a therapeutic agent against H5N1 influenza virus infection. siRNA specific for influenza virus nucleoprotein (NP) mRNA was employed as the key antiviral agent to inhibit viral replication in this study. A humanized single- chain Fv antibody (huscFv) against the hemagglutinin (HA) of H5N1 highly pathogenic avian influenza virus (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells (the HA target cells). The huscFv was applied to cationic polyethylene glycol- conjugated 3 beta -[N-(N', N'- dimethylaminoethane) carbamoyl] cholesterol- dioleoylphosphatidyl ethanolamine (PEGylated DC- Chol- DOPE) liposomes to generate immunoliposomes for siRNA delivery. The immunoliposomes were shown to specifically bind HA- expressing Sf9 cells and demonstrated enhanced siRNA transfection efficiency. The siRNA transfection efficiency was significantly reduced after preincubation of the HA target cells with an excess amount of free huscFv. These results therefore demonstrated that the enhanced siRNA delivery by use of immunoliposomes was mediated via targeting by huscFv. Furthermore, the siRNA silencing effect was more pronounced when the immunoliposomes were administered 6 to 12 h postH5N1 infection in MDCK cells compared with the nontargeted liposomes. This proof- of- concept study may contribute to the future design and development of an siRNA delivery system for combating viral infectious diseases in humans.
Funding Sponsor
National Nanotechnology Center of the National Science and Technology Development Agency, Thailand; Research Grant for Graduate Studies, Faculty of Medicine Siriraj Hospital, Mahidol University; Thailand Graduate Institute of Science and Technology Scholarship, National Science and Technology Development Agency, Thailand
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