TY - JOUR
T1 - An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors
AU - Motegi, Yukari
AU - Katayama, Kazufumi
AU - Sakurai, Fuminori
AU - Kato, Takuya
AU - Yamaguchi, Tomoko
AU - Matsui, Hayato
AU - Takahashi, Masahide
AU - Kawabata, Kenji
AU - Mizuguchi, Hiroyuki
N1 - Funding Information:
This study was supported by Grants-in-Aid for Research on Publicly Essential Drugs and Medical Devices from the Japan Health Sciences Foundation to K.K. and H.M ( KHB1009 ).
PY - 2011/7/30
Y1 - 2011/7/30
N2 - Viral vectors expressing short hairpin RNA (shRNA) are attractive for efficient and tissue-specific RNA interference (RNAi) delivery. We and others previously reported that recombinant adenovirus (Ad) vector-mediated RNAi has great potential for a variety of applications in molecular biology studies and gene therapy. In the present study, we have developed an efficient Ad vector-mediated RNAi system, in which an Ad vector carries four shRNA-expression cassettes (Ad-multi-shRNA vector), a simple and effective strategy for enhancing the RNAi response per Ad vector particle. The data demonstrated that the Ad-multi-shRNA vectors showed an enhanced RNAi effect compared to conventional Ad vectors containing a single shRNA-expression cassette. An application of the Ad-multi-shRNA vector carrying four same shRNA-sequences against the RET finger protein, an oncogene known to desensitize cells to oxidative stress and cisplatin, resulted in an enhanced cytotoxic effect of cisplatin, demonstrating the advantages of the Ad-multi-shRNA vector for silencing target genes. Furthermore, an Ad-multi-shRNA carrying four different shRNA-sequences efficiently silenced the multiple target genes simultaneously. These data suggest the potential usefulness of the Ad-multi-shRNA vector not only in basic research but also in clinical gene therapy.
AB - Viral vectors expressing short hairpin RNA (shRNA) are attractive for efficient and tissue-specific RNA interference (RNAi) delivery. We and others previously reported that recombinant adenovirus (Ad) vector-mediated RNAi has great potential for a variety of applications in molecular biology studies and gene therapy. In the present study, we have developed an efficient Ad vector-mediated RNAi system, in which an Ad vector carries four shRNA-expression cassettes (Ad-multi-shRNA vector), a simple and effective strategy for enhancing the RNAi response per Ad vector particle. The data demonstrated that the Ad-multi-shRNA vectors showed an enhanced RNAi effect compared to conventional Ad vectors containing a single shRNA-expression cassette. An application of the Ad-multi-shRNA vector carrying four same shRNA-sequences against the RET finger protein, an oncogene known to desensitize cells to oxidative stress and cisplatin, resulted in an enhanced cytotoxic effect of cisplatin, demonstrating the advantages of the Ad-multi-shRNA vector for silencing target genes. Furthermore, an Ad-multi-shRNA carrying four different shRNA-sequences efficiently silenced the multiple target genes simultaneously. These data suggest the potential usefulness of the Ad-multi-shRNA vector not only in basic research but also in clinical gene therapy.
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U2 - 10.1016/j.jconrel.2011.04.009
DO - 10.1016/j.jconrel.2011.04.009
M3 - Article
C2 - 21515317
AN - SCOPUS:79960097145
SN - 0168-3659
VL - 153
SP - 149
EP - 153
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 2
ER -