Review Article | Published:

mRNA-based therapeutics — developing a new class of drugs

Nature Reviews Drug Discovery volume 13, pages 759780 (2014) | Download Citation

Abstract

In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.

Key points

  • Messenger RNA (mRNA) is a pivotal molecule of life, involved in almost all aspects of cell biology.

  • As the subject of basic and applied research for more than 5 decades, mRNA has only recently come into the focus as a potentially powerful drug class able to deliver genetic information.

  • Synthetic mRNA can be engineered to resemble mature and processed mRNA molecules as they occur naturally in the cytoplasm of eukaryotic cells and to transiently deliver proteins.

  • Recent advances addressed challenges inherent to this drug class and provided the basis for a broad spectrum of applications

  • Besides cancer immunotherapies and infectious disease vaccines novel approaches such as in vivo delivery of mRNA to replace or supplement proteins, mRNA-based induction of pluripotent stem cells, or mRNA-assisted delivery of designer nucleases for genome engineering rapidly emerged and entered into pharmaceutical development.

  • This Review gives a comprehensive overview of the current state of mRNA drug technologies, their applications and crucial aspects relevant to mRNA based drug discovery and development.

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Affiliations

  1. TRON Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany.

    • Ugur Sahin
    •  & Özlem Türeci
  2. BioNTech Corporation, An der Goldgrube 12, 55131 Mainz, Germany.

    • Ugur Sahin
    •  & Katalin Karikó
  3. Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

    • Katalin Karikó

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Competing interests

U.S. is an inventor of multiple patents related to mRNA therapeutics. He is co-founder and CEO of the biotechnology company BioNTech (Mainz, Germany), which focuses on the development of mRNA therapies.

K.K. is an inventor of several patents related to mRNA technologies. She is an employee and the vice president of mRNA drug development in the BioNTech Incorporation (Mainz, Germany).

O.T. is an inventor of several patents related to mRNA technologies.

Corresponding authors

Correspondence to Ugur Sahin or Katalin Karikó or Özlem Türeci.

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