Utilization of a PNA-peptide conjugate to induce a cancer protease-responsive RNAi effect

被引:2
作者
Lee, Eun Kyung [1 ]
Kim, Chan Woo [2 ]
Kawanami, Hiroyuki [1 ]
Kishimura, Akihiro [1 ,2 ,3 ,4 ]
Niidome, Takuro [2 ]
Mori, Takeshi [1 ,2 ,3 ]
Katayama, Yoshiki [1 ,2 ,3 ,4 ,5 ]
机构
[1] Kyushu Univ, Grad Sch Syst Life Sci, Nishi Ku, Fukuoka 8190395, Japan
[2] Kyushu Univ, Fac Engn, Dept Appl Chem, Nishi Ku, Fukuoka 8190395, Japan
[3] Kyushu Univ, Ctr Future Chem, Nishi Ku, Fukuoka 8190395, Japan
[4] Kyushu Univ, Int Res Ctr Mol Syst, Nishi Ku, Fukuoka 8190395, Japan
[5] Kyushu Univ, Ctr Adv Med Innovat, Higashi Ku, Fukuoka 8128582, Japan
关键词
APTAMER-SIRNA CHIMERAS; DOUBLE-STRANDED-RNA; RIBONUCLEOTIDE REDUCTASE; CATHEPSIN-B; M2; SUBUNIT; IN-VITRO; INTERFERENCE; DELIVERY; THERAPY; THERAPEUTICS;
D O I
10.1039/c5ra17737e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Small interfering RNA (siRNA) is regarded as a promising tool for cancer therapy because of the wide applicability to various cancer-related genes. However, non-specific delivery of siRNA is one of the major causes of adverse effects. To access the issue, here we designed a new siRNA system which turns on RNAi responding to a cancer cell-specific protease, cathepsin B. The system uses a peptide nucleic acid (PNA)-peptide conjugate to provide this protease-responsive activation. The PNA-peptides were found to form hybrids with double-stranded RNAs with complementary protruding regions, which then affected the susceptibility of dsRNA to Dicer. The dsRNA/PNA-peptide hybrids were activated in cancer cells with a high cathepsin B activity to show RNAi.
引用
收藏
页码:85816 / 85821
页数:6
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