A research group from Japan has developed a method to produce highly active mRNA vaccines at high purity using a unique cap to easily separate the desired capped mRNA.
Reviewed by Lily Ramsey, LLMOct 10 2023 This 'Purecap' technique extracted up to 100% pure Cap2-type mRNA, which showed 3-4 times better production of the protein that stimulates the immune system. These results open up the possibility of purer vaccines with a lower risk of inflammation caused by impurities. Their findings were published in Nature Communications.
Impurities in mRNA vaccines are often introduced in the capping stage. During this stage, a cap structure is added that improves the translation of mRNA and protects and stabilizes it. Caps can only be added to single-stranded mRNA, so ideally a vaccine should contain 100% pure single-stranded mRNA. However, unwanted double-strands of mRNA may be present, reducing its purity.
A research group led by Professor Hiroshi Abe , Project Assistant Professor Masahito Inagaki , and Project Associate Professor Naoko Abe of the Graduate School of Science, Nagoya University, in collaboration with Tokyo Medical and Dental University, used a unique PureCap method to introduce a hydrophobic tag at the capping stage. The tagged mRNA was easily separated at the RP-HPLC stage. The tag was then easily removed by light treatment, resulting in a 98%-100%-pure vaccine.
"The Cap structure used in mRNA vaccines has so far been limited to Cap0 and Cap1 types. However, we used our technique to manufacture Cap0, Cap1, and Cap2-type structures," Abe said. "Highly purified Cap0, Cap1, and Cap2-type mRNA synthesized using the PureCap method showed lower immunostimulatory activity compared to mRNAs synthesized using conventional techniques showing their potential use in pharmaceuticals.
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