(361b) Biophysical Characterization Platform for AAV-Based Gene Therapy Products

Adeno-associated virus (AAV) based gene therapy offers new hope to treating rare diseases such as the rare forms of hemophilia and blindness. Although Food and Drug Administration has recently approved first AAV-based therapeutics for genetic blindness, there are limited number of studies designed to evaluate the drug product formulation of AAVs that ensures the long-term stabilities and activities of the vectors. In this study, we focus on the implementation of state-of-the-art characterization methodologies, including differential scanning fluorimetry (DSF), isothermal titration calorimetry, dynamic light scattering (DLS), zeta potential, high performance liquid chromatography (HPLC), and atomic force microscopy (AFM) to better assess the AAV biophysical and biochemical stability in various formulations. In addition, we are seeking biophysical understanding of the stabilization mechanism of several stabilizing agents and define a stable biophysical condition for AAV formulation such as pH, ionic strength and stabilizing agents. The development and implementation of the characterization platform enable us to define optimal formulation maintaining biophysical and biochemical stabilities of AAVs spontaneously, and it is essential to control and improve the critical attributes of AAV formulation for driving the product and process understanding of AAV based gene therapy.