Abstract:
Adeno-associated virus(AAV) has emerged as a pivotal vector for gene therapy products due to its safety and high efficiency. Currently, numerous AAV-based gene therapy products are in clinical stages, with eight drugs based on recombinant AAV vectors approved by the Food and Drug Administration(FDA) and European Medicines Agency(EMA). Gene therapy products utilizing AAV typically have a high viral genome titer, which can lead to aggregation in the formulation, rendering the drug inactive. This study investigated the stability of a gene therapy product based on serotype 2 recombinant adeno-associated virus(rAAV2) under various prescriptions and stress conditions(25±2)°C, 5 freeze-thaw cycles, and light exposure. Identified the optimal prescription by evaluating key quality attributes of the samples, including appearance, viral genome titer, solid rate, purity, and specific titer. The stability study results indicated that a formulation containing 10 mmol·L
−1 Tris buffer, 180 mmol·L
−1 sodium chloride, 0.001% Poloxamer 188, and pH 7.5 exhibited the best performance. This paper detailed the process and results of the prescription development for rAAV2 gene therapy products and offered a reference for the development of similar rAAV products.