Novel Long RNA Manufacturing Approaches for Advancing RNA Therapeutics

Biotech, Drug Discovery & Development, Fundamental Research, Life Science, Pharma, Pharma Manufacturing & Supply Chain,
  • Tuesday, October 21, 2025 | 10am EDT (NA) / 3pm BST (UK) / 4pm CEST (EU-Central)
  • 60 min

Recently, demands in RNA manufacturing for long-chain RNAs exceeding 100 nucleotides, such as single guide RNA (sgRNA) for genome editing, have been increasing. Generally, these types of RNA are longer than traditional chemically synthesized oligonucleotides.

Many challenges can be encountered during the chemical synthesis of long-chain RNA, such as the steric hindrance of the TBDMS (tert-butyldimethylsilyl) protecting group on RNA phosphoramidite monomers. In addition, in vitro transcription is widely used in long-chain RNA synthesis but cannot be utilized when any partial base modifications are required; for example, if uridine is to be replaced with pseudouridine, all uridines must be replaced.

To address these challenges, an efficient method was developed for manufacturing a high-quality long-chain RNA by enzymatic ligation from multiple chemically synthesized short-chain RNA fragments. The enzyme used was T4 RNA ligase 2, also known as dsRNA ligase. To ligate RNAs with this enzyme, it is necessary to form a nick-like structure at the joining site using complementary DNA splints. When two sequences of RNA are used, DNA splints that form complementary strands of several to 20 bases around the joining site are designed.

However, this method is not efficient for ligating fragments of three or more sequences. A highly efficient synthesis of long RNA was established through enzymatic ligation by designing short DNA splints to form complementary strands towards all short RNA fragments. This method was also applicable to the synthesis of 100-base-length RNAs with chemical modifications partially. Furthermore, a 560 base length mRNA encoding a protein was successfully synthesized, and a functional protein was synthesized by a cell-free translation system using this mRNA.

This solution for the production of long-stranded RNA allows for chemical modifications and is expected to lead to the development of nucleic acid drugs, which have previously not been possible as drug discovery targets due to chemical synthesis limitations.

Register for this webinar to learn how innovative long RNA manufacturing approaches can drive the development of next-generation RNA medicines.

Speaker

Masato Sanosaka, Ajinomoto Bio-Pharma Services

Masato Sanosaka, Group Leader of Research and Process Development, Ajinomoto Bio-Pharma Services

Dr. Masato Sanosaka is a Group Leader of Research and Process Development at Ajinomoto Bio-Pharma Services. He received his PhD in Agricultural Science from Tohoku University in 2008. During his postdoctoral training, he investigated cell biology, mitochondrial biology and innate immunity. After that, he joined GeneDesign, Inc. in 2015, which became a part of Aji Bio-Pharma in 2019. In his current role, Dr. Sanosaka focuses on the development of synthetic methods for long-chain RNA using biochemical and molecular biological approaches.

Message Presenter

Who Should Attend?

This webinar will appeal to:

  • Directors/Managers of RNA therapeutics development
  • Process Development Scientists & Engineers
  • Oligonucleotide & mRNA Researchers
  • Molecular Biologists & Biochemists
  • Formulation Scientists focused on RNA delivery
  • Quality & Analytical Development Specialists in nucleic acid production
  • Business Development & Strategic Leaders evaluating RNA-based platforms

What You Will Learn

Attendees will:

  • Understand the limitations of current methods (chemical synthesis and IVT) for long-chain RNA production and the challenges with base modifications
  • Learn about a novel enzymatic ligation approach using T4 RNA ligase 2 and DNA splints to efficiently assemble multiple RNA fragments into long-chain RNA
  • Explore case studies, including successful synthesis of 100-mer RNAs with partial chemical modifications and a 560-base mRNA that produced functional protein
  • Gain insights into new opportunities for drug discovery, including how this method opens the door to nucleic acid therapeutics that were previously inaccessible due to synthesis constraints
  • See future applications of enzymatic ligation in developing next-generation RNA medicines

Xtalks Partner

Ajinomoto Group

The Ajinomoto Group is a global company focused on the research, development, and manufacture of high quality products for the pharmaceutical, specialty chemical, nutraceutical, sports nutrition, and health & beauty industries, as well as food seasonings and consumer food products. Headquartered in Tokyo, the Ajinomoto Group has over 34,000 employees, maintaining operations in 36 countries and regions, and possessing a global production network of 117 factories. In fiscal 2022, sales were JPY 1,359 billion (USD 10.1 billion). Ajinomoto Bio-Pharma Services (Aji Bio-Pharma) is a fully integrated contract development and manufacturing organization (CDMO) with sites in Belgium, United States, Japan and India providing comprehensive development, cGMP manufacturing and aseptic fill finish services for small and large molecule APIs and intermediates.

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