Current status and future perspectives on MRNA drug manufacturing

Webb, Cameron and Ip, Shell and Bathula, Nuthan V. and Popova, Petya and Soriano, Shekinah K. V. and Ly, Han Han and Eryilmaz, Burcu and Nguyen Huu, Viet Anh and Broadhead, Richard and Rabel, Martin and Villamagna, Ian and Abraham, Suraj and Raeesi, Vahid and Thomas, Anitha and Clarke, Samuel and Ramsay, Euan C. and Perrie, Yvonne and Blakney, Anna K. (2022) Current status and future perspectives on MRNA drug manufacturing. Molecular Pharmaceutics, 19 (4). pp. 1047-1058. ISSN 1543-8384 (https://doi.org/10.1021/acs.molpharmaceut.2c00010)

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Abstract

The coronavirus disease of 2019 (COVID-19) pandemic launched an unprecedented global effort to rapidly develop vaccines to stem the spread of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). Messenger ribonucleic acid (mRNA) vaccines were developed quickly by companies that were actively developing mRNA therapeutics and vaccines for other indications, leading to two mRNA vaccines being not only the first SARS-CoV-2 vaccines to be approved for emergency use but also the first mRNA drugs to gain emergency use authorization and to eventually gain full approval. This was possible partly because mRNA sequences can be altered to encode nearly any protein without significantly altering its chemical properties, allowing the drug substance to be a modular component of the drug product. Lipid nanoparticle (LNP) technology required to protect the ribonucleic acid (RNA) and mediate delivery into the cytoplasm of cells is likewise modular, as are technologies and infrastructure required to encapsulate the RNA into the LNP. This enabled the rapid adaptation of the technology to a new target. Upon the coattails of the clinical success of mRNA vaccines, this modularity will pave the way for future RNA medicines for cancer, gene therapy, and RNA engineered cell therapies. In this review, trends in the publication records and clinical trial registrations are tallied to show the sharp intensification in preclinical and clinical research for RNA medicines. Demand for the manufacturing of both the RNA drug substance (DS) and the LNP drug product (DP) has already been strained, causing shortages of the vaccine, and the rise in development and translation of other mRNA drugs in the coming years will exacerbate this strain. To estimate demand for DP manufacturing, the dosing requirements for the preclinical and clinical studies of the two approved mRNA vaccines were examined. To understand the current state of mRNA-LNP production, current methods and technologies are reviewed, as are current and announced global capacities for commercial manufacturing. Finally, a vision is rationalized for how emerging technologies such as self-amplifying mRNA, microfluidic production, and trends toward integrated and distributed manufacturing will shape the future of RNA manufacturing and unlock the potential for an RNA medicine revolution.

  • Item type:Article
    ID code:80195
    Dates:
    Date
    Event
    4 April 2022
    Published
    3 March 2022
    Published Online
    18 February 2022
    Accepted
    Notes:This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
    Subjects:Medicine > Therapeutics. Pharmacology
    Science > Microbiology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:13 Apr 2022 15:18
    Last modified:19 Apr 2024 00:29
    URI:https://strathprints.strath.ac.uk/id/eprint/80195
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