ABSTRACT:
The field of mRNA therapeutics is rapidly developing across a wide range of applications, including infectious diseases, rare disorders, protein replacement, and cancer immunotherapy. Central to the production of mRNA is in vitrotranscription (IVT), a method that relies on an RNA polymerase to synthesize mRNA from a DNA template. However, the quality and efficiency of this process depends heavily on the RNA polymerase used. Key performance indicators such as yield, integrity, purity, capping efficiency, and the presence of double-stranded RNA (dsRNA) are directly influenced by the RNA polymerase, impacting manufacturing costs, dosage requirements and potential adverse events. The commonly used T7 RNA polymerase (“T7”), although widespread, has limitations that make it suboptimal for pharmaceutical-grade mRNA production.
To address these challenges, Primrose Bio (“Primrose”) has developed an ultra high-throughput enzyme evolution platform resulting in the first of a series of proprietary high-performing RNA polymerases, Prima RNApols™, that are distinct from T7. These enzymes are engineered to translate various template types, including linear, synthetic, circular, and self-amplifying RNAs, as well as a range of cap structures and modified nucleotides. This permits customized, efficient mRNA synthesis tailored to the unique demands of next-generation vaccines and therapeutics. Prima RNApols™ ExTend Cap AU has been developed for maximizing yield and cap incorporation efficiency of self-amplifying RNA (saRNA). It consistently outperforms T7 across multiple IVT metrics, delivering higher yields, better RNA integrity, lower dsRNA levels, and better cap incorporation efficiency using less cap analog. These features make this enzyme ideal for producing high-quality mRNA at scale and at lower cost.
Primrose’s Prima RNApols™ represent a significant advancement in mRNA manufacturing, offering a superior alternative to legacy enzymes, ultimately enhancing the scalability, quality, and customization of mRNA therapeutics for the future of medicine.