Poster presentation at the 10th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan [Development of a Mild Cleavage and Deprotection Method for RNA Oligonucleotides Containing Universal Support]
We gave a poster presentation at the 10th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan, held at Kobe International Exhibition Hall No. 2 from July 1st to 3rd, 2025, and we would like to introduce the content published in the abstracts collection.
Presentation
| Title | Development of a Mild Cleavage and Deprotection Method for RNA Oligonucleotides Containing Universal Support |
| Presenter | Takaki Habuchi Research & Development Department, Health & Medical Business Division, NIPPON SHOKUBAI CO., LTD. |
Background
Universal solid supports, such as UnyLinker*1, have been widely used in solid-phase oligonucleotide synthesis because they enable oligonucleotide synthesis regardless of the type of nucleic acid and ligand at the 3′-end. As a result, they help reduce costs and facilitate inventory control. Furthermore, because the atoms of universal linkers are not incorporated into any significant structural fragment of the drug substance, they are not classified as starting materials in manufacture, thereby reducing the burden of quality control. On the other hand, the slow removal rate of universal supports from the oligonucleotide requires strong basic conditions, which can lead to the degradation of RNA-containing oligonucleotides.
Research Contents
In order to solve this problem, we developed a cleavage and deprotection (C&D) method for RNA-containing oligonucleotides that promotes the removal of UnyLinker and inhibits RNA degradation. We initially investigated the organic solvents added to the C&D solutions to suppress degradation of RNA. As a result, we found that certain solvents suppressed RNA degradation while strongly removing UnyLinker and protecting groups at the base moiety. Subsequently, we screened the additives*2 to promote the removal of UnyLinker and identified those that removed it effectively. Finally we demonstrated that our new C&D method, which combines these organic solvents and metal salts, significantly removes UnyLinker adducts and inhibits RNA degradation. From the above results, we achieved to obtain the high-quality RNA oligonucleotides using UnyLinker.
*1 UnyLinker is a trademark of Ionis Pharmaceuticals, Inc.
*2 Nelson, P. S. et al., BioTechniques 1997, 22, 725–756.
Meeting Information
| Name | The 10th Annual Meeting of the Nucleic Acids Therapeutics Society of Japan |
| Meeting | July 1st (Tue) – July 3rd (Thu), 2025 |
| Venue | Kobe International Exhibition Hall No. 2 |
| Official website | https://www.natsj.jp/2025/natsj10 |