Rapid and Ultra-Pure mRNA Production with Next-Generation RNA Polymerases

PROJECT SUMMARY Cisterna Biologics is addressing critical challenges in mRNA purification for therapeutic applications by developing a novel production and purification process. This Phase I SBIR aims to generate ultra-pure mRNA, essential for high-dosage and frequent administration in treatments ranging from enzyme replacement to cancer immunotherapy. Traditional in vitro transcription (IVT) methods using T7 RNA polymerase produce significant byproducts that can trigger adverse immune responses. In collaboration with the University of Texas-Austin, Cisterna's approach involves the development of cold-adapted (psychrophilic) RNA polymerases (RNAPs), which maintain high activity at low temperatures and reduce byproduct formation. Additionally, Cisterna's proprietary SPEcific Capture and Cleavage (SPECC) purification technology intends to eliminate contaminants completely. The Phase I SBIR project will demonstrate the capability of this technology to synthesize contaminant-free mRNA, improving safety and efficacy for therapeutic use. Initial aims include optimizing psychrophilic RNAPs and synthetic promoters to minimize contaminants significantly, with the ultimate goal of replacing current gold-standard purification methods. The successful completion of this phase will pave the way for Phase II, focusing on scaling up manufacturing and validating the platform in clinical settings. As the mRNA therapeutics market is projected to grow substantially, Cisterna plans to establish itself as a leader in high-quality mRNA production, leveraging its technologies and potential partnerships with biotech and pharmaceutical companies.