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 two complementary approaches aimed at reducing the concentration of dsRNA contaminating mRNA solutions.
The first approach of Nuntius biotechnology consists of using an additive, during in vitro transcription, which prevents the synthesis of the complementary strand of the mRNA and consequently the formation of dsRNA. Thus, this first approach alone decreases the amount of dsRNA by 170-fold.
The second approach is to specifically capture dsRNA, which was produced during transcription. This approach alone reduces the amount of dsRNA produced during transcription by 233-fold.
The combination of both approaches is possible and decreases the amount of dsRNA by 4,955-fold.
Nuntius is compatible with other approaches aimed at reducing the concentration of dsRNA. These can alternatively be replaced by Nuntius.