Using analytical centrifugation to develop life-changing gene therapies

Gene therapies are emerging with the potential to treat or cure some of the most challenging diseases currently facing medicine. The molecular precision of gene therapies requires accurate and reliable characterization of multiple materials during manufacturing, including delivery methods such as lipid nanoparticles and viral vectors.

Understanding viral vector packaging is important to ensure that gene therapies are safe and effective. If vectors are empty or partially full and lacking therapeutic genes, there may be an adverse immune response and patient morbidity. But separating empty, intermediate and full viral capsids during the purification process can be challenging. Ion exchange or other types of chromatography may be serotype-dependent, influenced by capsid external proteins and binding kinetics. Preparatory density gradient ultracentrifugation, with instruments such as the Beckman Coulter Life Sciences Optima XPN Ultracentrifuge, allows high-quality, serotype-agnostic purification that costs less per batch than chromatography approaches.

While preparatory ultracentrifugation can separate and isolate vectors, still necessary to quantify loading efficiencies of viral vectors. Preparing the purified material for subsequent analyses involves labor-intensive steps, which makes the process inherently slow and inefficient.

Advances in analytical techniques have facilitated the development of density gradient equilibrium analytical ultracentrifuge (DGE-AUC) methods, which combine the high-resolution benefits of density gradient ultracentrifugation purification with analytical techniques. The Beckman Coulter Life Sciences Optima AUC can be used to generate data on empty/full analyses for viral vectors, allowing researchers to understand batch quality as well as distinguishing numbers of full vs. partially filled capsids. Actionable, repeatable quality control is key to scaling up production and availability of viral vector-mediated gene therapies. Streamlining and enhancing workflows unlocks productivity and improves quality.

At the Life Sciences companies of Danaher, we take a holistic approach to gene therapy analytics to meet your throughput needs. To learn more about our offerings or explore ways of partnering with us, contact an expert at the Life Sciences companies of Danaher today.