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Mechanistic Modeling of In Vitro Transcription
  • Richard Braatz,
  • Nathan Merica Stover,
  • Krystian Ganko
Richard Braatz
Massachusetts Institute of Technology

Corresponding Author:[email protected]

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Nathan Merica Stover
Massachusetts Institute of Technology
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Krystian Ganko
Massachusetts Institute of Technology
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Abstract

The in vitro transcription (IVT) reaction used in the production of mRNA vaccines and therapies remains poorly quantitatively understood. Mechanistic modeling of IVT could inform reaction design, scale up, optimization, and control. In this work, we develop a mechanistic model of IVT to include nucleation and growth of magnesium pyrophosphate crystals and subsequent agglomeration of crystals and DNA. A novel quantitative description is included for the rate of transcription as a function of target sequence length, DNA concentration, and T7 polymerase concentration. The model explains previously unexplained trends in IVT data and quantitatively predicts the effect of adding the pyrophosphatase enzyme to the reaction system. The model is validated on additional literature data showing an ability to predict transcription rates as a function of RNA sequence length.
25 Aug 2023Submitted to Biotechnology and Bioengineering
25 Aug 2023Assigned to Editor
25 Aug 2023Submission Checks Completed
25 Aug 2023Review(s) Completed, Editorial Evaluation Pending
29 Sep 2023Reviewer(s) Assigned
16 Nov 2023Editorial Decision: Revise Major