mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

• Published in: Biomedicines Vol. 10; no. 1; p. 50
• Main Authors: Ouranidis, Andreas, Vavilis, Theofanis, Mandala, Evdokia, Davidopoulou, Christina, Stamoula, Eleni, Markopoulou, Catherine K, Karagianni, Anna, Kachrimanis, Kyriakos
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.12.2021; MDPI
• Subjects: Automation; Cell cycle; Chimeric antigen receptors; Clinical trials; Cost control; COVID-19; Design of experiments; Drug dosages; formulation; Genomes; Good Manufacturing Practice; Immunization; Immunogenicity; Laboratories; lipid nanoparticle; Lymphocytes T; Manufacturing; mRNA; mRNA vaccines; nanomedicine; Pandemics; Peptides; pharma industry 4.0; Pharmaceutical industry; Proteins; Quality control; Quality standards; Reproducibility; Review; Severe acute respiratory syndrome coronavirus 2; Shelf life; Somatic cells; therapeutics; Vaccines; lipid nanoparticle; therapeutics; CAR T-cell; formulation; mRNA vaccines; nanomedicine; mRNA; storage; pharma industry 4.0; protein replacement
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10010050

In the quest for a formidable weapon against the SARS-CoV-2 pandemic, mRNA therapeutics have stolen the spotlight. mRNA vaccines are a prime example of the benefits of mRNA approaches towards a broad array of clinical entities and druggable targets. Amongst these benefits is the rapid cycle "from design to production" of an mRNA product compared to their peptide counterparts, the mutability of the production line should another target be chosen, the side-stepping of safety issues posed by DNA therapeutics being permanently integrated into the transfected cell's genome and the controlled precision over the translated peptides. Furthermore, mRNA applications are versatile: apart from vaccines it can be used as a replacement therapy, even to create chimeric antigen receptor T-cells or reprogram somatic cells. Still, the sudden global demand for mRNA has highlighted the shortcomings in its industrial production as well as its formulation, efficacy and applicability. Continuous, smart mRNA manufacturing 4.0 technologies have been recently proposed to address such challenges. In this work, we examine the lab and upscaled production of mRNA therapeutics, the mRNA modifications proposed that increase its efficacy and lower its immunogenicity, the vectors available for delivery and the stability considerations concerning long-term storage.