tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2014 Mar 10. [Epub ahead of print]
Targeted siRNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection.
Khantasup K1, Kopermsub P, Chaichoun K, Dharakul T.
Author information
Abstract
This study describes a proof of concept study on the use of 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 (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells. The huscFv was decorated onto cationic 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 pre-incubation of the HA target cells with an excess amount of free huscFv. These results therefore demonstrated that the enhanced siRNA delivery of immunoliposomes was mediated via targeting by huscFv. Furthermore, the siRNA silencing effect was more pronounced when the immunoliposomes were administered 6-12 h post H5N1 infection in MDCK cells, compared with the non-targeted liposomes. This proof of concept study may contribute to the future design and development of a siRNA delivery system for combating viral infectious diseases in humans.
PMID:
24614365
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24614365
Targeted siRNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection.
Khantasup K1, Kopermsub P, Chaichoun K, Dharakul T.
Author information
Abstract
This study describes a proof of concept study on the use of 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 (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells. The huscFv was decorated onto cationic 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 pre-incubation of the HA target cells with an excess amount of free huscFv. These results therefore demonstrated that the enhanced siRNA delivery of immunoliposomes was mediated via targeting by huscFv. Furthermore, the siRNA silencing effect was more pronounced when the immunoliposomes were administered 6-12 h post H5N1 infection in MDCK cells, compared with the non-targeted liposomes. This proof of concept study may contribute to the future design and development of a siRNA delivery system for combating viral infectious diseases in humans.
PMID:
24614365
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24614365