Aji Bio-Pharma develops highly functional ancestral RNA ligase

Aji Bio-Pharma develops highly functional ancestral RNA ligase

This artificial RNA ligase has higher thermostability than natural RNA ligase

  • By IPP Bureau | February 23, 2023

Ajinomoto Bio-Pharma Services (Aji Bio-Pharma), a leading provider of biopharmaceutical contract development and manufacturing services, is pleased to announce the development of a new enzyme for double strand oligonucleotide formation with high productivity.

In collaboration with researchers from the University of Shizuoka, Aji Bio-Pharma succeeded in developing a highly functional artificial RNA ligase using the ancestral design method. It was found that this artificial RNA ligase has higher thermostability than natural RNA ligase as well as superior ligation activity for RNA fragments containing xenonucleic acid.

When using the natural RNA ligase for RNA fragments (including xenonucleic acid) as reaction substrates to synthesize a marketed siRNA drug substance, the yield was only 20% after 24 hours of reaction. In contrast, when using the highly functional artificial RNA ligase, the reaction yield improved to 80% under the same conditions, confirming that it has properties suitable for enzymatic synthesis of nucleic acid medicines. This approach attains more productive and environmentally safe oligonucleotide synthesis when compared to the conventional method.

"We are excited to provide new research to our partners and support them in their efforts to supply lifesaving therapeutics," said Yusuke Hagiwara, Senior Researcher, Ajinomoto Bioscience & Fine Chemicals Research Laboratories. "This discovery for siRNA is a great example of Aji Bio-Pharma continuing to provide reliable and innovative solutions to our clients."

The RNA fragments used as reaction substrates can be produced by not only conventional solid phase synthesis, but also by Ajinomoto Co.'s AJIPHASE® technology, especially in large quantities and with high purity. This achievement is expected to be applied as one of the technologies that enables the mass production of nucleic acid drugs with high efficiency and high purity. This result was presented in the journal "Applied and Environmental Microbiology" published by the American Society for Microbiology.

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