King of Prussia, Pennsylvania
Tosoh Bioscience, a renowned leader in the field of chromatography, announced the recent publication of a groundbreaking paper titled "Separation of Full and Empty AAV Capsids by Anion-Exchange Chromatography Using Choline-Type Salts." The research, made accessible to the scientific community through SSRN/Elsevier as a pre-print publication, spotlights an innovative analytical method for professionals working with Adeno-Associated Viruses (AAVs) that ensures a safer working environment and environmental protection. The method uses non-toxic choline chloride for the separation of empty and full AAV capsids, marking a significant improvement in comparison with the traditionally used, and highly toxic, tetramethylammonium chloride (TMAC).
Safety First: Tosoh Bioscience Transforms Gene Therapy with Innovative AAV Analysis Technique
Recombinant adeno-associated viruses (rAAVs) are indispensable in modern medicine. Their precise gene-editing capabilities have formed the foundation of FDA and EMA-approved therapies like Luxturna® for retinal dystrophy, Zolgensma® for spinal muscular atrophy, and Hemgenix® for hemophilia B. As more than 300 rAAV-based products are in clinical trials, accurate, efficient, and safe analytical methods are paramount.
Jukka Kervinen, Head of Applications for the Americas, who has been invited to present this study at the BioProcessing Network conference in Australia, elaborates on the complexity of this situation: "The very nature of AAVs makes them challenging to study. Empty capsids, those without the therapeutic payload, can greatly reduce drug efficacy and raise potential health risks. Reliable quality control methods to separate these from the full capsids are critical, and anion-exchange (AEX) chromatography has risen as a highly selective technique. But with most AEX methods using toxic TMAC in the buffer composition, we faced a two-fold challenge: improving separation efficacy while ensuring the safety of the method."
Egbert Müller, Senior Scientific Advisor, is the mind behind the study. With years of experience in the field, he was the first to suggest exploring alternative compounds with structural resemblances to the ligand structure of Q-type AEX columns. "It dawned on me that we should identify a substance with a similar structure but without the hazardous profile of TMAC,” explained Müller. “That’s when we decided to delve deeper into choline chloride."
The outcome of the extensive research based on this initial idea is an innovative analytical method combining the high-performance TSKgel Q-STAT chromatography column with a buffer containing choline chloride. Sam Kurth, Application Scientist at Tosoh Bioscience, and a key player in the development phase, elaborated on the process. "The ambition was clear: advance the field without sidelining safety. Integrating choline chloride into the analytical process wasn’t just about swapping out one chemical for another. It required extensive development and validation to ensure the method's effectiveness and safety."
And the implications of this groundbreaking method are not just confined to safety. Romain Dabre, Associate Director of Global Product Management, shares the broader impact: "This isn't only about refining a method. It's about shaping the future of cell and gene therapy. By offering a more efficient and safer alternative for AAV analysis, we're empowering researchers and professionals globally. In essence, we're providing the tools needed for the scientific community to push boundaries without compromising the safety of their work. "
Key Takeaways:
• Empty AAV capsids, lacking therapeutic payloads, challenge the efficacy of gene therapies.
• AEX chromatography with toxic TMAC in the buffer composition is the current analytical method of choice.
• Tosoh's novel AEX chromatography method combines the TSKgel Q-STAT HPLC column and non-toxic choline chloride, phasing out the hazardous TMAC.
To read this revolutionary research and understand Tosoh Bioscience's continued commitment to innovation and safety, download the paper:
Separation of Full and Empty AAV Capsids by Anion-Exchange Chromatography Using Choline-Type Salts by Sam Kurth, Tianyu Li, Alana Hausker, William Evans, Romain Dabre, Egbert Muller, Jukka Kervinen :: SSRN