Laboratory of XNA Screening and Design
1. Members
| Project Leader | KASAHARA Yuuya |
|---|---|
| Project Researcher | HOSHINO Hidekazu |
| Researcher | ISHIDA Kenta |
| Research Assistant | YAMAGUMA Harumi, SENGA Yoko, KAMEOKA Natsumi, ASO Kotomi |
| Visiting Researcher | Soyoung Park, ODA Masayuki, INAGAKI Kyoko |
| PhD Student | MITAMURA Rei (D1) |
| Research Trainee | ODA Chihiro (D2), TAMENORI Yusuke (B6), NITATOUGE Kaito (D1), YOSHIMURA Shunsuke (B5), IINUMA Kouta (B3) |
2. Background and objectives
In recent years, artificial nucleic acid (Xeno nucleic acid; XNA) developed by chemical technology has served as a medicine. To date, 16 types of nucleic acid drugs have been approved in Japan, the United States, and Europe. For example, antisense nucleic acids such as "Spinraza" and "Viltepso" and siRNAs such as "Onpattro" control the translation of target mRNA into protein. In addition, nucleic acid aptamer such as "Macugen" binds to the target protein and regulates its activity. As described above, there are various types of nucleic acid drug, and it is possible to target almost all the molecules existing in the living body such as DNA, RNA and protein. Nucleic acid drug leads to the development of a specific drug for intractable diseases that are difficult to treat with existing methods. In this project, synthesis of XNA to be introduced into nucleic acid drug such as antisense oligonucleotides and nucleic acid aptamers, and screening of sequence, and target specific nucleic acid is developed. In addition, we aim to create practical nucleic acid drugs by designing and optimizing the isolated hit molecules according to the application.
3. Overview of our research
Antisense oligonucleotides require characteristics such as binding affinity for target RNA, in vivo stability, intracellular migration and safety. Likewise, nucleic acid aptamers require characteristics such as in vivo stability, safety, binding affinity to target proteins, inhibitory activity, and retention in the body. In this project, we are developing XNA that modified the base part, sugar part, phosphoric acid part of nucleic acid to contain the above characteristics. We are also developing new screening methods that can efficiently screen active sequences from candidate sequence libraries. Especially in screening of nucleic acid aptamers, we are developing polymerase mutants that can extend XNAs. In this way, we conduct research aiming at the development of nucleic acid drug for various diseases including intractable rare diseases by consistently doing from synthesis of artificial nucleic acid to screening.
Laboratory of XNA Screening and Design
| y-kasahara*nibiohn.go.jp (replace * by @) |