Publication: Targeted small interfering RNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection
Issued Date
2014-01-01
Resource Type
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-84898669965
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.58, No.5 (2014), 2816-2824
Suggested Citation
Kannika Khantasup, Phikulthong Kopermsub, Kridsada Chaichoun, Tararaj Dharakul Targeted small interfering RNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection. Antimicrobial Agents and Chemotherapy. Vol.58, No.5 (2014), 2816-2824. doi:10.1128/AAC.02768-13 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/34724
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Title
Targeted small interfering RNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection
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 3β-[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 post-H5N1 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. Copyright © 2014, American Society for Microbiology.