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

Abstract

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.

COVID-19 vaccines adverse events: potential molecular mechanisms

“…Some of the advantages of mRNA-based vaccines include the fast-track manufacturing process, the inability of mRNA to integrate to the host cell’s genome, reduced contamination issues, biodegradability, and elicitation of robust humoral and cellular immunity, thus acting concomitantly as both an immunogen and an adjuvant [ 18 , 20 , 128 – 130 ]. However, mRNA products present stability issues which might be considered a major obstacle for worldwide distribution [ 129 , 130 ]. Furthermore, data for the extent of the trapped mRNA inside the LNPs are not currently available [ 130 ].…”

coupled Hydrodynamic Flow Focusing (cHFF) to Engineer Lipid–Polymer Nanoparticles (LiPoNs) for Multimodal Imaging and Theranostic Applications

“…Thus, microfluidic technology has the features to tackle the issue of the development of nanostructures and support the optimal design of the delivery systems, improving nanoparticle–biological interaction and guiding new designs and delivery strategies. The recent success of pharmaceutical nano-formulations is pushing towards the development of quality-oriented bottom-up manufacturing processes to face the challenging scale-up to commercial production volumes of conventional production methods [ 70 ]. Indeed, in the translation of manufacturing conditions from laboratory to an industrial scale, the conventional bulk mixing devices are characterised by variability and heterogeneity within and between batches that results in sub-optimal control of quality attributes of end-products.…”

Downregulation of LOC441461 Promotes Cell Growth and Motility in Human Gastric Cancer

“…Second, modulating the activity of transcription factors interacting with LOC441461 could be a candidate therapeutic target to manage advanced gastric cancer. Recently, RNA biopharmaceuticals have been attracting attention as a breakthrough clinical application of the COVID-19 RNA vaccine [ 33 , 61 ]. Proving its application as a gastric cancer treatment by regulating the expression of LOC441461 will be a very interesting study in the future.…”