The synthesis of a messenger RNA (mRNA) is achieved by in vitro transcription of a gene, thanks to a phage RNA polymerase. This mRNA possesses a cap analog at its 5’ end, which is involved in translation as well as mRNA stability. The phage RNA polymerase incorporates this cap analog during the initiation of transcription.
Unfortunately, capping lowers the yield of mRNA synthesis and cap analogs are expensive. Thus, it is tempting not to add a cap analog to the transcription mixture. However, the absence of cap greatly decreases the level and duration of protein expression achieved by mRNA in transfected cells.
Messenger Biopharma has shown that two RNA elements fully take the place of cap analog. The first RNA element protects mRNA against RNases at least as efficiently as a cap. The duration of protein expression achieved by our uncapped mRNA is similar to that of capped mRNA. A second RNA element initiates translation at least as efficiently as a cap analog.
The level of protein expression achieved by our uncapped mRNA in transfected mouse skin is 9.3-fold higher than that achieved by capped mRNA.Thus, Aegis™ biotechnology consists in replacing an expensive cap analog by RNA sequences, leading to a 30-fold drop of the cost of mRNA synthesis and higher levels of protein expression in vivo.
This biotechnology has been patented in May 2018.