Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines

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Despite their widespread use, intracellular studies of mRNA vaccines have been limited. Using direct RNA Oxford Nanopore sequencing, researchers uncovered a novel mechanism enhancing mRNA vaccine performance: re-adenylation by TENT5A. This enzyme extends mRNA poly-A tails to boost mRNA stability and antigen production. This study showcases how nanopore sequencing enables real-time, single-molecule insights into mRNA metabolism — offering a strategy to improve future RNA-based therapeutics.

Key points:

  • Krawczyk et al. used Oxford Nanopore direct RNA sequencing to study the poly-A tails of individual therapeutic mRNA molecules

  • The results showed that therapeutic mRNAs can have their poly-A tails extended within cells. This increases their stability and production of coded antigens, potentially explaining the efficacy of existing mRNA vaccines

  • By exploring the immune response to mRNA vaccination, they identified the biological mechanism for the poly-A extension — re-adenylation by TENT5A

  • The findings reveal a principal that could be harnessed to improve the efficacy of mRNA therapeutics in the future

Sample type: mouse tissue

Kit: cDNA-PCR Barcoding Kit, cDNA-PCR Sequencing Kit, Direct RNA Sequencing Kit

Authors: Paweł S. Krawczyk, Michał Mazur, Wiktoria Orzeł, Olga Gewartowska, Sebastian Jeleń, Wiktor Antczak, Karolina Kasztelan, Aleksandra Brouze, Katarzyna Matylla-Kulińska, Natalia Gumińska, Bartosz Tarkowski, Ewelina P. Owczarek, Kamila Affek, Paweł Turowski, Agnieszka Tudek, Małgorzata Sroka, Tomasz Śpiewla, Monika Kusio-Kobiałka, Aleksandra Wesołowska, Dominika Nowis, Jakub Golab, Joanna Kowalska, Jacek Jemielity, Andrzej Dziembowski, Seweryn Mroczek
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PubMed
Workflow overview: direct RNA sequencing
  • Published on: April 16 2025
  • Source: Nature