ABSTRACT
Although mRNA vaccines have been published in 1993 by a French team (Prof. Meulien, Paris), their development has been hindered by the prejudice associated to the supposed fragility of mRNA. Actually, mRNA is a very robust biomolecule (it can be heated up to 90 degrees, frozen, lyophilized), easy to manufacture even at high scale and capable to lead to potent protein expression once administered naked or in nanoparticle formulations. Private investments in companies (for example CureVac created in 2000, BioNTech created in 2008 and Moderna created in 2011) have allowed to develop the potential of mRNA based therapies. The safety, versatility and efficacy of mRNA-based vaccines was evidenced during the COVID-19 pandemic: less than one year after the publication of the sequence of SARS-CoV-2, an mRNA vaccine against COVID-19 was approved and marketed. More mRNA vaccines (against infectious diseases and cancer) are in clinical developments and are expected to be approved in the coming years. In addition, mRNA-based therapies using non-immunogenic formulations of mRNA are being developed. Thus, the potential of synthetic mRNA in medicine is just starting to be unraveled and this versatile biomolecule is expected to be the active pharmaceutical ingredient in many future prophylactic and therapeutic drugs. Copyright © 2022 Elsevier B.V.
ABSTRACT
Synthetic mRNA acts as a template for synthesizing proteins, protein fragments, or peptides and now has many pharmaceutical applications.1,2 Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel zoonotic RNA virus, has resulted in the rapid development of dedicated mRNA vaccines.3–5 This rapid response was made possible by using mRNA platforms that already existed for experimental vaccines against other infectious diseases and cancer.6–12 Carrier-based mRNA vaccines have been developed using lipid-based delivery, peptide-based delivery, polymer-based delivery, and cationic nano-emulsions, as well as dendritic cells.13 The mRNA vaccine leads to the expression of encodedantigensinantigen-presentingcells(APCs),generatingbothinnateandadaptiveimmuneresponses.Futuredevelopments in mRNA therapy in oncology are expected to include adaptations in the routes of administration and co-delivery of multiple mRNAs with other anti-cancer treatments, such as immune checkpoint inhibitors (ICI), radiotherapy, or chemotherapy. In addition, advances in next-generation sequencing (NGS) technology allow the genome, exome, and transcriptome of a single cancer patient to be deciphered. This new knowledge about the diversity of epitopes in different tumors and corresponding specific T cells has allowed the advancement of personalized cancer treatments.14 The article aims to present the rationale for the new therapeutic roles of mRNA vaccines, from COVID-19 and other infections to personalized oncology therapeutics. © 2021 Healthbook TIMES Oncology Hematology. All rights reserved.