Showing 1 - 1 of 1 results for "20144"
- ReferenceJ. Nelson et al. (jun 2020) Science advances 6 26 eaaz6893
Impact of mRNA chemistry and manufacturing process on innate immune activation.
Messenger RNA (mRNA) represents an attractive therapeutic modality for potentially a wide range of clinical indications but requires uridine chemistry modification and/or tuning of the production process to prevent activation of cellular innate immune sensors and a concomitant reduction in protein expression. To decipher the relative contributions of these factors on immune activation, here, we compared, in multiple cell and in vivo models, mRNA that encodes human erythropoietin incorporating either canonical uridine or N1-methyl-pseudouridine (1m$\Psi$), synthesized by either a standard process shown to have double-stranded RNA (dsRNA) impurities or a modified process that yields a highly purified mRNA preparation. Our data demonstrate that the lowest stimulation of immune endpoints was with 1m$\Psi$ made by the modified process, while mRNA containing canonical uridine was immunostimulatory regardless of process. These findings confirm that uridine modification and the reduction of dsRNA impurities are both necessary and sufficient at controlling the immune-activating profile of therapeutic mRNA. View PublicationCatalog #: Product Name: 17858 EasySep™ Human CD14 Positive Selection Kit II 70500 Human Peripheral Blood Leukopak, Fresh 20144 EasySep™ Buffer Catalog #: 17858 Product Name: EasySep™ Human CD14 Positive Selection Kit II Catalog #: 70500 Product Name: Human Peripheral Blood Leukopak, Fresh Catalog #: 20144 Product Name: EasySep™ Buffer
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