Tomita-Sudo Elisa, Akita Tomoka, Sakimoto Nae, Tahara-Takamine Saori, Kawakami Junji
Konan Laboratory for Oligonucleotide Therapeutics (KOLOT), 7-1-20 Minatojima-Minamimachi, Kobe 650-0047, Japan.
Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Kobe 650-0047, Japan.
Int J Mol Sci. 2024 Dec 10;25(24):13240. doi: 10.3390/ijms252413240.
2',4'-methylene bridged nucleic acid/locked nucleic acid (2',4'-BNA/LNA; LNA) is a modified nucleic acid that improves the function of antisense oligonucleotide therapeutics. In particular, LNA in the DNA strand increases its binding affinity for the target RNA. Predicting the binding affinities of LNA-containing antisense oligonucleotides and RNA duplexes is useful for designing antisense oligonucleotides. The nearest neighbor parameters may be useful for binding affinity prediction, similar to those for natural nucleic acids. However, the sequence dependence of the thermodynamic stability of DNA/RNA duplexes containing LNA remains unexplored. Therefore, in this study, we evaluated the thermodynamic stabilities of DNA/RNA duplexes containing a single LNA modification in the DNA strand. We found that LNA-stabilized DNA/RNA duplexes averaged -1.5 kcal mol. Our findings suggest that the thermodynamic stabilization effect of LNA is sequence-specific.
2',4'-亚甲基桥连核酸/锁核酸（2',4'-BNA/LNA；LNA）是一种修饰的核酸，可改善反义寡核苷酸疗法的功能。特别是，DNA链中的LNA增加了其对靶RNA的结合亲和力。预测含LNA的反义寡核苷酸与RNA双链体的结合亲和力对于设计反义寡核苷酸很有用。最近邻参数可能类似于天然核酸的参数，对结合亲和力预测有用。然而，含LNA的DNA/RNA双链体热力学稳定性的序列依赖性仍未得到探索。因此，在本研究中，我们评估了在DNA链中含有单个LNA修饰的DNA/RNA双链体的热力学稳定性。我们发现LNA稳定的DNA/RNA双链体平均为-1.5千卡/摩尔。我们的研究结果表明，LNA的热力学稳定作用具有序列特异性。
