RNA interference silences the human papillomavirus 6b/11 early gene E7 in vitro and in vivo.
BACKGROUND
RNA interference (RNAi) is a potential therapeutic tool in the treatment of various diseases, such as cancers and viral infections. Silencing of E7 genes is an effective method to suppress human papilloma virus (HPV)-related tumours.


OBJECTIVE
To determine the therapeutic potential of RNAi in controlling condyloma acuminatum (CA).


METHODS
Small interfering (si)RNA duplexes or small-hairpin (sh)RNA-expressing plasmids targeting the E7 genes of HPV-6b or HPV-11were inoculated into cultured E7-expressing cells via cationic liposomes, or into E7 gene-expressing mouse tumour models intratumorally or intravenously. Experiments were performed in triplicate and E7 mRNA level was analysed by real-time PCR.


RESULTS
The in vitro experiments found that both siRNAs and shRNA-expressing plasmids reduced the mRNA levels of HPV-6b or HPV-11 E7 to 20-40% at the optimum dosage of 25-50 nmol/L for siRNAs and 0.1-0.2 microg/mL for shRNA-expressing vectors. The optimum time for this to happen was 72 h. E7 mRNA expression in tumour models was reduced to 45-50% after three intratumural injections. Intratumoral injections of RNAi effectors induced greater inhibition than did intravenous injections.


CONCLUSIONS
We conclude that HPV-6b/11 E7 gene expression can be specifically modulated by RNAi, which may provide a useful method in the management of CA.
Chen
X Z
XZ
Department of Dermatology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou City, China.
Zhu
K J
KJ
Xu
Y
Y
Tang
X Y
XY
Cai
X Z
XZ
Zhang
X
X
Cheng
H
H
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D020868:Gene Silencing; D052140:Human papillomavirus 11 / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000628:therapy* / Q000821:virology
D034741:RNA, Small Interfering