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Poster Presentations
Day 4, June 25（Wed.）
Room P (Maesato East, Foyer, Ocean Wing)
- 4P-AM-27（3A-O2-1455）
Multimass Analysis of Adeno-Associated Virus Vectors by Orbitrap-Based Charge Detection Mass Spectrometry
(1Osaka Univ., 2Shimadzu Corp., 3Osaka Univ. Shimadzu AIRL, 4U-Medico Inc.)
oRyoji Nakatsuka1,2,3, Yuki Yamaguchi1, Kiichi Hirohata1, Saki Shimojo1, Makoto Murakami1, Mark Allen Rocafort4, Yasuo Tsunaka1, Mitsuko Fukuhara1,4, Tetsuo Torisu1, Susumu Uchiyama1
Recombinant adeno-associated virus (rAAV) plays a crucial role as a vector in gene therapy. To ensure the safety of rAAV-based therapeutics, it is essential to evaluate its critical quality attributes (CQAs). These CQAs include the relative quantification of impurity particles lacking the genome of interest, the analysis of genome length encapsidated within rAAV, and the stoichiometric evaluation of viral proteins (VPs) composing the capsid. However, a comprehensive method for assessing these CQAs has not yet been established.
In this study, we employed charge detection mass spectrometry (CD-MS), which simultaneously measures charge and mass-to-charge ratio to determine ion mass, for the evaluation of rAAV CQAs. We demonstrated that CD-MS enables a comprehensive assessment of multiple CQAs, including (1) relative quantification of impurity particles, (2) direct analysis of encapsidated genomes, and (3) estimation of viral protein stoichiometry. Our findings provide new insights into the properties of AAV vectors and contribute to addressing the critical challenge of ensuring their quality for effective gene therapy applications.