doi_________::c166d06aeaed817937a79a400906a4b9 2023-03-09T00:12:02.045Z 2023-03-09T00:24:00.8Z
50|openapc_____::c166d06aeaed817937a79a400906a4b9 10.3390/pr9111967 pr9111967 50|doiboost____::c166d06aeaed817937a79a400906a4b9 3209532762 10.3390/pr9111967 Digital Twins for Continuous mRNA Production 2021-11-04 The global coronavirus pandemic continues to restrict public life worldwide. An effective means of limiting the pandemic is vaccination. Messenger ribonucleic acid (mRNA) vaccines currently available on the market have proven to be a well-tolerated and effective class of vaccine against coronavirus type 2 (CoV2). Accordingly, demand is presently outstripping mRNA vaccine production. One way to increase productivity is to switch from the currently performed batch to continuous in vitro transcription, which has proven to be a crucial material-consuming step. In this article, a physico-chemical model of in vitro mRNA transcription in a tubular reactor is presented and compared to classical batch and continuous in vitro transcription in a stirred tank. The three models are validated based on a distinct and quantitative validation workflow. Statistically significant parameters are identified as part of the parameter determination concept. Monte Carlo simulations showed that the model is precise, with a deviation of less than 1%. The advantages of continuous production are pointed out compared to batchwise in vitro transcription by optimization of the space–time yield. Improvements of a factor of 56 (0.011 µM/min) in the case of the continuously stirred tank reactor (CSTR) and 68 (0.013 µM/min) in the case of the plug flow reactor (PFR) were found. Process Chemistry and Technology Chemical Engineering (miscellaneous) Bioengineering Coronavirus medicine.disease_cause medicine Continuous production Messenger RNA Continuous stirred-tank reactor Plug flow reactor model Mathematics In vitro transcription Biological system Yield (chemistry) Public life 03 medical and health sciences 0301 basic medicine 030104 Developmental Biology 0303 health sciences 030304 Developmental Biology 02 engineering and technology 0210 nano-technology 021001 Nanoscience & Nanotechnology 01 natural sciences 0104 chemical sciences 010405 Organic Chemistry 2021-11-05 2021-11-04 Crossref 2146.08 EUR Processes false false 0.9 null 2021-11-04 10.3390/pr9111967 https://creativecommons.org/licenses/by/4.0/ https://doi.org/10.3390/pr9111967