A Novel Approach to Eliminate Length Impurities for High-Quality mRNA Production

PROJECT SUMMARY With the success of mRNA-based Covid vaccines, there is immense interest in leveraging mRNA technology to develop therapeutics for previously untreatable diseases. However, therapeutic applications, such as protein replacement therapy, cardiovascular regeneration, and cancer immunotherapy, require mRNA of exceptional purity to ensure safety and efficacy. Current mRNA production methods often yield mRNA with impurities, such as double-stranded RNA (dsRNA), long RNA (LRNA), and short truncated (stRNA), which can provoke immune responses and compromise therapeutic outcomes. Cisterna has developed an innovative platform capable of synthesizing high-quality, purified mRNA, devoid of product-related contaminants, making it ideal for therapeutic use while ensuring consistency and reproducibility across batches. In this Phase I SBIR, our goal is to demonstrate the efficacy of our technology in eliminating dsRNA, LRNA, and stRNA compared to conventional methods. We will employ sensitive fluorescence-based methods and assays to quantify and eliminate these impurities, enabling the production of highly pure therapeutic mRNA. Furthermore, we will validate our technology by assessing its impact on immunogenic response and protein expression in mice, aiming for minimal to no immune activation while maintaining or enhancing therapeutic efficacy. Successful completion of this project will provide a validated production platform for contaminant-free mRNA synthesis, paving the way for Phase II studies focused on target identification, construct design, and scale-up manufacturing. The mRNA therapeutics market is poised for significant growth, with biotech and pharmaceutical companies actively developing mRNA-based therapeutics. We aim to leverage potential partnerships to position ourselves as a key player in this dynamic field.