Enzymatic Ligation Technology
Enzymatic ligation builds a full-length RNA from short, high-purity fragments joined by an enzyme. We apply this approach in two ways: enzymatic siRNA synthesis for scalable and flexible manufacturing, and GenClip™ for long RNA from 100 to 500 mer.
Two Applications of Enzymatic Ligation
Both approaches begin with shorter, high-purity fragments that are joined enzymatically, supporting siRNA synthesis at manufacturing scale and long RNA synthesis from 100 to 500 mer.
Enzymatic siRNA Synthesis
Best For: Large-Scale and complex/multivalent siRNA synthesis
Approach: siRNA assembled from short sense and antisense fragments by enzymatic ligation
Fragment Joining: Complementary sense and antisense fragments anneal directly, eliminating the need for a separate guide strand
Key Advantage: Reduced N±1 impurities, fewer purification steps, and manufacturing flexibility through a fragment-based approach
GenClip™ Long RNA Synthesis
Best For: Long RNA, including sgRNA, pre-miRNA, and mRNA
Approach: Long RNA synthesis from 100 to 500 mer
Fragment Joining: Short DNA splints align RNA fragments for enzymatic ligation
Key Advantage: Combines solid-phase synthesis and enzymatic ligation to support yield and quality for longer RNA sequences
Enzymatic siRNA Synthesis
Our enzymatic siRNA technology utilizes enzyme-mediated ligation of four or more RNA fragments to produce target siRNA compounds through a scalable, fragment-based approach. The RNA fragments can be synthesized using AJIPHASE™ or SPOS and are joined using our proprietary ligation enzyme, designed to accommodate a broad range of modified nucleic acids. A quality-focused control strategy integrates high-purity crude fragment production, ligation process development, and simplified downstream purification, reducing the need for individual purification of sense and antisense fragments and supporting consistent product quality.
Patent: WO2020171092 — Method for Producing Modified Oligonucleotide Including Complementary Sequence
GenClip™ Long RNA Synthesis
GenClip™ enables the synthesis of long RNA (100–500 mer) with high yield and high quality. It is also usable for the synthesis of sgRNA, pre-miRNA and mRNA, and due to its high quality, long RNA produced with GenClip™ can also be used as analytical standards.
The combination of solid-phase synthesis and enzymatic ligation enables higher yield than conventional methods, and GenClip™ is applicable to various chemical modifications such as 2′-F, 2′-MOE and LNA. GenClip™ is currently available for research use (Non-GMP); GMP manufacturing is under development.
Patent: WO2024048684 — Method for Producing Nucleic Acid Molecule
Let’s Discuss Enzymatic Ligation
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siRNA at scale. Long RNA with high quality.