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

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