Liquid phase process for the preparation of oligonucleotides

By using nucleoprotective base groups (NPGs) to protect building blocks in liquid-phase oligonucleotide synthesis, the concentration polarization problem in LPOS technology is solved, achieving efficient membrane separation and purification, suitable for industrial-scale oligonucleotide preparation.

CN122422331APending Publication Date: 2026-07-17EXACTMER LTD

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
EXACTMER LTD
Filing Date
2024-06-14
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Existing membrane-assisted liquid-phase oligonucleotide synthesis (LPOS) technology is prone to concentration polarization at high concentrations, leading to increased viscosity and aggregation, resulting in inefficient membrane separation and fouling problems.

Method used

Using building blocks protected by nucleoprotective groups (NPGs), grown oligonucleotides are separated by membrane filtration, reducing the effects of concentration polarization. Building blocks protected by nucleoprotective groups (NPGs) reduce viscosity and aggregation during membrane filtration, and the frequency and position of the group Q are adjusted to accommodate changes in oligonucleotide length.

Benefits of technology

This technology enables efficient membrane separation at high concentrations, reduces pollution, and allows for the direct preparation of oligonucleotides with increased length on an industrial scale, thereby improving synthesis efficiency and purity.

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Abstract

本发明涉及制备寡核苷酸的液相方法。更具体地,本发明涉及制备寡核苷酸的膜过滤辅助液相方法,其中用于生长寡核苷酸的一个或多个构建块包含被核碱基保护性基团(NPG)保护的核碱基,其中NPG包含基团Q。本发明人已经确定,作为膜辅助LPOS技术的一部分,使用其中核碱基包含核碱基保护性基团(NPG)的构建块显著减少了低效膜分离和 / 或污染的情况。
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