Weighing the DNA Content of Adeno-Associated Virus Vectors with Zeptogram Precision Using Nanomechanical Resonators
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katsikis_NL_2022.pdf
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Author(s)
Katsikis, Georgios
Hwang, Iris E
Wang, Wade
Bhat, Vikas S
McIntosh, Nicole L
Karim, Omair A
Blus, Bartlomiej J
Sha, Sha
Agache, Vincent
Wolfrum, Jacqueline M
Date Issued
2022
Journal
Nano Letters
Publisher
American Chemical Society (ACS)
Citation
Katsikis, Georgios, Hwang, Iris E, Wang, Wade, Bhat, Vikas S, McIntosh, Nicole L et al. 2022. "Weighing the DNA Content of Adeno-Associated Virus Vectors with Zeptogram Precision Using Nanomechanical Resonators." Nano Letters, 22 (4).
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Author's final manuscript
Abstract
Quantifying the composition of viral vectors used in vaccine development and gene therapy is critical for assessing their functionality. Adeno-associated virus (AAV) vectors, which are the most widely used viral vectors for in vivo gene therapy, are typically characterized using PCR, ELISA, and analytical ultracentrifugation which require laborious protocols or hours of turnaround time. Emerging methods such as charge-detection mass spectroscopy, static light scattering, and mass photometry offer turnaround times of minutes for measuring AAV mass using optical or charge properties of AAV. Here, we demonstrate an orthogonal method where suspended nanomechanical resonators (SNR) are used to directly measure both AAV mass and aggregation from a few microliters of sample within minutes. We achieve a precision near 10 zeptograms which corresponds to 1% of the genome holding capacity of the AAV capsid. Our results show the potential of our method for providing real-time quality control of viral vectors during biomanufacturing.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Mechanical Engineering
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1021/ACS.NANOLETT.1C04092
