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.