RNA Oncological Therapeutics: Intracellular Hairpin RNA Assembly Enables MicroRNA-Triggered Anticancer Functionality

• DOI: 10.1021/jacs.3c09524
• Publication Date: 2024-01-03T16:12:56Z
• Authors: Kunihiko Morihiro; Shunto Morita; Naoki Harada; Manami Baba; Jongmin Yum; Mitsuru Naito; Kanjiro Miyata; Genta Nagae; Akimitsu Okamoto
• Keywords: RNA Silencing

RNA therapeutics are of global interest because their versatility in targeting a variety intracellular and extracellular biomolecules. In that context, long double-stranded (dsRNA) has been studied as an antitumor agent activates the immune response. However, its performance is constrained by poor cancer selectivity cell-penetration ability. Here, we designed synthesized oncolytic hairpin pair (oHP) was selectively cytotoxic toward cells expressing abundant oncogenic microRNA-21 (miR-21). Although structure each thermodynamically metastable, catalytic miR-21 input triggered it to open generate nicked dsRNA. We demonstrated oHP functioned amplifier information presence various tumor-bearing mice. This work represents first example use short molecules build-up-type anticancer agents miRNA.