NC State, in partnership with NIST and Pfizer, aims to pioneer the combination of multi-attribute method (MAM) mass spectrometry and ion mobility spectrometry (IMS) into the gene therapy space. Modality-targeted development will provide the specificity and speed necessary to meet the emerging demands of process development and set the industry standard for product knowledge and control.
By combining MAM and IMS in gene therapy, this project will enable increased speed, resolution, and robustness of analytical and biological methods to characterize gene therapy products, which can lead to better control of product quality.
Increased speed, resolution, and robustness of analytical and biological methods to characterize gene therapy products, which can lead to better control of product quality
By leveraging the capabilities delivered by NC State University’s Biomanufacturing Training and Education Center (BTEC)—producing 2.6 × 10¹⁵ capsids (AAV2-GFP) and advanced characterization technologies such as accelerated Multi-Attribute Method workflows, LC-IMS-MS structural analysis, and streamlined transduction assays—organizations can reduce analytical and process development costs by minimizing sample requirements and manual labor. These interoperable, high-throughput workflows accelerate product knowledge generation and time-to-market while ensuring superior quality and regulatory compliance through precise impurity detection (<0.1%), robust attribute-specific performance criteria, and repeatable transduction assays—all while maintaining scalability and GMP standards.
Generated an industry-grade AAV2 suitable for analytical method innovation
MAM-based purity test with limit of detection (Target < 0.5 % Impurity)
MAM-based attribute-specific control for modification susceptible peptides (Target
Develop first-of-its-kind IMS VP subunit assay (Target throughput
Enable quality-by-design of future AAV materials via an associated transduction assay (repeatability target < 30 and intermediate precision target < 40% CV)
Ryan, J. P., Kostelic, M. M., Hsieh, C., Powers, J., Aspinwall, C., Dodds, J. N., Schiel, J. E., Marty, M. T., & Baker, E. S. (2023). Characterizing Adeno-Associated Virus Capsids with Both Denaturing and Intact Analysis Methods. Journal of the American Society for Mass Spectrometry, 34(12), 2811-2821. https://doi.org/10.1021/jasms.3c00321
Ryan, J., Baker, E., Gilleskie, G., Smith-Moore, C. M., Powers, J., & Schiel, J., Characterization and Differentiation of Adeno-Associated Virus (AAV) Serotypes Using Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS), Virtual, September 16, 2021.
Ryan, J., Baker, E., Schiel, J., Gilleskie, G., & Smith-Moore, C. M., Characterization and Differentiation of Adeno-Associated Virus (AAV) Serotypes Using Ion Mobility Spectrometry-Mass Spectrometry (IMS-MS), 69th Annual ASMS (American Society for Mass Spectrometry) Conference, Philadelphia, PA, November 2, 2021.
Expanding AAV Process and Characterization Analytical Technologies (PC2.2-120), NIIMBL Member Forum, Virtual, November 18, 2021.
Schiel, J., Mass Spectrometry as a Critical Gene Therapy Characterisation Technology, Cambridge Healthtech Institute’s Bioprocessing Summit Europe, Virtual, March 16, 2021.
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North Carolina State University
Federal Stakeholder: National Institute of Standards and Technology
Pfizer, Inc.
