New highly potent and specific E6 and E7 siRNAs for treatment of HPV16 positive cervical cancer

被引：0
作者：
K Yamato
T Yamada
M Kizaki
K Ui-Tei
Y Natori
M Fujino
T Nishihara
Y Ikeda
Y Nasu
K Saigo
M Yoshinouchi
机构：
[1] Molecular Cellular Oncology and Microbiology,Division of Pathology
[2] Graduate School,Division of Hematology
[3] Tokyo Medical and Dental University,Department of Biophysics and Biochemistry
[4] Keio University,Department of Oral Microbiology
[5] School of Medicine,Department of Urology
[6] Keio University,Department of Physiology
[7] School of Medicine,undefined
[8] Graduate School of Science,undefined
[9] University of Tokyo,undefined
[10] RNAi Company Ltd.,undefined
[11] Kyushu Dental College,undefined
[12] Okayama University Graduate School of Medicine,undefined
[13] Dentistry,undefined
[14] and Pharmaceutical Science,undefined
[15] Okayama University Graduate School of Medicine,undefined
[16] Dentistry,undefined
[17] and Pharmaceutical Science,undefined
来源：
Cancer Gene Therapy | 2008年 / 15卷
关键词：
siRNA therapy; HPV16; cervical cancer;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Persistent infection by high-risk types of human papillomaviruses (HPV) is a necessary cause of cervical cancer, with HPV16 the most prevalent, accounting for more than 50% of reported cases. The virus encodes the E6 and E7 oncoproteins, whose expression is essential for maintenance of the malignant phenotype. To select efficacious siRNAs applicable to RNAi therapy for patients with HPV16+ cervical cancer, E6 and E7 siRNAs were designed using siDirect computer software, after which 10 compatible with all HPV16 variants were selected, and then extensively examined for RNAi activity and specificity using HPV16+ and HPV16−cells. Three siRNAs with the highest RNAi activities toward E6 and E7 expression, as well as specific and potent growth suppression of HPV16+ cancer cells as low as 1 nM were chosen. Growth suppression was accompanied by accumulation of p53 and p21WAF1/CIP1, as well as morphological and cytochemical changes characteristic of cellular senescence. Antitumor activity of one of the selected siRNAs was confirmed by retarded tumor growth of HPV16+ cells in NOD/SCID mice when locally injected in a complex with atelocollagen. Our results demonstrate that these E6 and E7 siRNAs are promising therapeutic agents for treatment of virus-related cancer.
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页码：140 / 153
页数：13
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