The present invention relates to a method for synthesizing an
RNA molecule of a given sequence, comprising the step of determining the fraction (1) for each of the four nucleotides G, A, C and U in said
RNA molecule, and the step of synthesizing said
RNA molecule by
in vitro transcription in a sequence-optimized reaction mix, wherein said sequence-optimized reaction mix comprises the four
ribonucleoside triphosphates GTP, ATP, CTP and UTP, wherein the fraction (2) of each of the four
ribonucleoside triphosphates in the sequence-optimized reaction mix corresponds to the fraction (1) of the respective
nucleotide in said
RNA molecule, a buffer,
a DNA template, and an
RNA polymerase. Further, the present invention relates to a
bioreactor (1) for synthesizing RNA molecules of a given sequence, the
bioreactor (1) having a reaction module (2) for carrying out
in vitro RNA transcription reactions in a sequence-optimized reaction mix, a capture module (3) for temporarily capturing the transcribed RNA molecules, and a control module (4) for controlling the infeed of components of the sequence-optimized reaction mix into the reaction module (2), wherein the reaction module (2) comprises a
filtration membrane (21) for separating nucleotides from the reaction mix, and the control of the infeed of components of the sequence-optimized reaction mix by the control module (4) is based on a measured concentration of separated nucleotides.