Nuntius
In vitro transcription by T7 RNA polymerase leads to the formation of double-stranded RNA (dsRNA), which is highly immunogenic.
Indeed, dsRNA activates TLR3, RIG-I and MDA5. Transduction signals from these receptors trigger the release of type I-interferon, as well as pro-inflammatory cytokines. Besides, dsRNA activates PKR and OAS leading to translation repression of transfected mRNA.
Messenger Biopharma has developed a technology aimed at reducing the concentration of dsRNA contaminating mRNA solutions.
Nuntius involves using a compound that is added to the in vitro transcription mixture.
This additive prevents the synthesis of the complementary strand of the mRNA and consequently the formation of dsRNA by interacting with T7 RNA polymerase.
It can be produced on a large scale and according to cGMPs.
This make it possible not to use N1-methyl-pseudouridine-5′-triphosphate to reduce the immunogenicity of the dsRNA.
The cost of mRNA synthesis linked to the use of this modified nucleotide is greater than that of UTP plus that of the additive.
This means that not only does Nuntius decrease the amount of dsRNA, but it also decreases the cost of mRNA synthesis.
This technology can be used for the production of capped and uncapped mRNA.
Nuntius is compatible with other approaches aimed at reducing the concentration of dsRNA, such as HPLC.
