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Cap-Independent Circular mRNA Translation Efficiency

Andrei A Deviatkin1,2, Ruslan A Simonov1,3, Kseniya A Trutneva1,2

  • 1Life Sciences Research Center, Moscow Institute of Physics and Technology, National Research University, 141700 Dolgoprudniy, Russia.

Vaccines
|February 28, 2023
PubMed

Insights

Circular messenger RNA (mRNA) vaccines offer enhanced stability over traditional mRNA vaccines by eliminating vulnerable ends. This review explores cap-independent translation initiation for developing novel circular mRNA vaccines and biotechnological products.

Area of Science:

  • Biotechnology
  • Vaccinology
  • Molecular Biology

Background:

  • Messenger RNA (mRNA) vaccines are pivotal in infectious disease control.
  • Conventional mRNA vaccines face instability issues due to exoribonucleases, necessitating specialized storage and limiting accessibility.
  • The five-prime and three-prime ends of linear mRNA are susceptible to degradation, impacting vaccine efficacy and shelf-life.

Purpose of the Study:

  • To review current knowledge on cap-independent translation initiation methods for circular mRNAs.
  • To discuss the potential of circular mRNA technology in developing more stable and accessible vaccines.
  • To explore applications of circular mRNAs in biotechnology beyond vaccines.

Main Methods:

  • Literature review of existing research on mRNA stability and translation.
  • Analysis of cap-independent translation initiation mechanisms.
  • Comparative assessment of linear versus circular mRNA platforms for vaccine development.

Main Results:

  • Circular mRNAs lack the vulnerable 5' and 3' ends, conferring inherent stability.
  • Canonical translation initiation is not possible with circular mRNAs due to the absence of a 5' cap.
  • Various cap-independent translation initiation strategies exist and are being investigated.

Conclusions:

  • Circular mRNA technology presents a promising avenue for overcoming the stability limitations of current mRNA vaccines.
  • Further research into cap-independent translation is crucial for realizing the full potential of circular mRNA vaccines.
  • Circular mRNAs could revolutionize vaccine development and other biotechnological applications by improving stability and accessibility.
Keywords:
cap-independent translationcircRNAmRNA vaccines

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