| RRC ID |
77857
|
| 著者 |
Morihiro K, Morita S, Harada N, Baba M, Yum J, Naito M, Miyata K, Nagae G, Okamoto A.
|
| タイトル |
RNA Oncological Therapeutics: Intracellular Hairpin RNA Assembly Enables MicroRNA-Triggered Anticancer Functionality.
|
| ジャーナル |
J Am Chem Soc
|
| Abstract |
RNA therapeutics are of global interest because of their versatility in targeting a variety of intracellular and extracellular biomolecules. In that context, long double-stranded RNA (dsRNA) has been studied as an antitumor agent that activates the immune response. However, its performance is constrained by poor cancer selectivity and cell-penetration ability. Here, we designed and synthesized an oncolytic RNA hairpin pair (oHP) that was selectively cytotoxic toward cancer cells expressing abundant oncogenic microRNA-21 (miR-21). Although the structure of each hairpin RNA was thermodynamically metastable, catalytic miR-21 input triggered it to open to generate a long nicked dsRNA. We demonstrated that oHP functioned as a cytotoxic amplifier of information in the presence of miR-21 in various cancer cells and tumor-bearing mice. This work represents the first example of the use of short RNA molecules as build-up-type anticancer agents that are triggered by an oncogenic miRNA.
|
| 公開日 |
2024-1-3
|
| DOI |
10.1021/jacs.3c09524
|
| PMID |
38170469
|
| IF |
14.612
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
A549(RCB0098)
MRC-5(RCB0218)
B16 melanoma(RCB1283) |
