Tohoku University Technology: Artificial Nucleic Acid that Specifically Cleaves Target RNA: T19-347
Next-generation nucleic acid drug discovery technology with high activity and the ability to reduce off-target effects.
Conventional nucleic acid medicines undergo a 1:1 hybrid formation with target RNA and are digested themselves to exhibit therapeutic effects. Although efforts have been made to enhance efficacy and reduce off-target toxicity through drug delivery systems (DDS) and reductions in dosage, the trade-off problem with activity has been identified as a challenge that needs to be overcome to achieve the expected therapeutic effects. The technology of this invention features optimally designed oligochimeric artificial nucleic acids that, after forming hybrids with target RNA, can repeatedly undergo a catalytic cleavage cycle of RNase H-mediated cleavage and dissociation without being cleaved themselves. As a result, high activity (with therapeutic effects obtained at nM orders that are 20 to 200 times higher than conventional methods) and reduced off-target effects are anticipated. The patented technology includes this molecular design technique, which involves designing a DNA-RNA junction with a complementary chimeric molecule at the desired cleavage site of the target RNA, synthesizing DNA-PNA/PRNA, and observing specific RNA cleavage only at the junction site. The melting temperatures (Tm) before and after cleavage of the complex formed by this chimeric molecule and RNA fragment are 22.3°C and 18.8°C, respectively, allowing for rapid dissociation at body temperature and the manifestation of catalytic effects through recycling reactions.
- Company：Tohoku Techno Arch Co., Ltd.
- Price：Other
