Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The most commonly used polymerase for in vitro transcription of mRNA is T7 RNA polymerase (T7 RNAP), due to its high yield and the high fidelity of the transcripts produced. However, T7 RNAP can also create multiple byproducts, including immunostimulatory double-stranded RNAs (dsRNAs) that can affect potency and safety. Producing mRNA products with low innate immune stimulation suitable for therapeutic applications therefore requires stringent downstream purification processes, typically involving reversed-phase high-performance liquid chromatography (RP-HPLC) which is both costly and time-consuming. Now, Dousis et al. have rationally and computationally designed an improved double-mutant T7 RNAP (G47A + 884G). Studies in vitro and in mice showed that mRNA products synthesized by the mutant T7 RNAP exhibited substantially decreased dsRNA burden and cytokine generation compared with those synthesized by wild-type T7 RNAP, thereby eliminating the need for downstream RP-HPLC purification. This novel T7 RNAP therefore has the potential to streamline therapeutic mRNA production.
Prices may be subject to local taxes which are calculated during checkout
Nature Reviews Drug Discovery22, 19 (2023)
doi: https://doi.org/10.1038/d41573-022-00200-4
References
Dousis, A. et al. An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts. Nat. Biotechnol. https://doi.org/10.1038/s41587-022-01525-6 (2022)