The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Resolving Adeno-Associated Viral Particle Diversity With Charge Detection Mass Spectrometry
Open accessAbstract
Recombinant adeno-associated viruses (AAVs) are promising vectors for human gene therapy. However, current methods for evaluating AAV particle populations and vector purity are inefficient and low resolution. Here, we show that charge detection mass spectrometry (CDMS) can resolve capsids that contain the entire vector genome from those that contain partial genomes and from empty capsids. Measurements were performed for both single-stranded and self-complementary genomes. The self-complementary AAV vector preparation appears to contain particles with partially truncated genomes averaging at half the genome length. Comparison to results from electron microscopy with manual particle counting shows that CDMS has no significant mass discrimination in the relevant mass range (after a correction for the ion velocity is taken into account). Empty AAV capsids are intrinsically heterogeneous, and capsids from different sources have slightly different masses. However, the average masses of both the empty and full capsids are in close agreement with expected values. Mass differences between the empty and full capsids for both single-stranded and self-complementary AAV vectors indicate that the genomes are largely packaged without counterions.
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“The method is accurate and repeatable (<2% CV).”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [56]
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“Pierson and colleagues56 report successful resolution of empty, partially filled, and full capsids and quantification of capsid content using CDMS.”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [56]
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Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
Gao, G.-P., Alvira, M. R., Wang, L., Calcedo, R., Johnston, J., & Wilson, J. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182412299 · Cited by 1,520
Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection
Zincarelli, C., Soltys, S., Rengo, G., & Rabinowitz, J. E. (2008) · Molecular Therapy · doi:10.1038/mt.2008.76 · Cited by 1,490
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Studying noncovalent protein complexes by electrospray ionization mass spectrometry
Loo, J. A. (1997) · Mass Spectrometry Reviews · doi:10.1002/(sici)1098-2787(1997)16:1 · Cited by 1,152
Adeno-associated Virus Serotypes: Vector Toolkit for Human Gene Therapy
Wu, Z., Asokan, A., & Samulski, R. J. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.05.009 · Cited by 957
Self-citationUnraveling the Mechanism of Electrospray Ionization
Konermann, L., Ahadi, E., Rodriguez, A. D., & Vahidi, S. (2012) · Analytical Chemistry · doi:10.1021/ac302789c · Cited by 738
McCarty, D. M., Fu, H., Monahan, P. E., Toulson, C. E., Naik, P., & Samulski, R. J. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302134 · Cited by 547
de la Mora, J. F. (2000) · Analytica Chimica Acta · doi:10.1016/s0003-2670(99)00601-7 · Cited by 543
Self-complementary AAV vectors; advances and applications
McCarty, D. M. (2008) · Molecular Therapy · doi:10.1038/mt.2008.171 · Cited by 515
Aurnhammer, C., Haase, M., Müther, N., Mück-Häusl, M., Rauschhuber, C., Huber, I., Nitschko, H., Busch, U., Sing, A., Ehrhardt, A., et al. (2012) · Human Gene Therapy Methods · doi:10.1089/hgtb.2011.034 · Cited by 494
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Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
Adeno-associated virus capsid assembly is divergent and stochastic
Wörner, T. P., Bennett, A. D., Habka, S., Snijder, J., Friese, O. V., Powers, T. W., Agbandje‐McKenna, M., & Heck, A. J. R. (2021) · Nature Communications · doi:10.1038/s41467-021-21935-5 · Cited by 228
Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.010 · Cited by 185
Wörner, T. P., Snijder, J., Bennett, A., Agbandje-McKenna, M., Makarov, A. A., & Heck, A. J. R. (2020) · Nature Methods · doi:10.1038/s41592-020-0770-7 · Cited by 186
Applications of Charge Detection Mass Spectrometry in Molecular Biology and Biotechnology
Jarrold, M. F. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00377 · Cited by 163
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Metadata
- Authors
- Pierson, E. E., Keifer, D. Z., Asokan, A., & Jarrold, M. F.
- Affiliations
- Indiana University Bloomington (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Asokan, Aravind
- Jarrold, Martin F.
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-06-16
- Volume
- 88
- Issue
- 13
- Pages
- 6718-6725
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- PMC
- PMC6537880
- OpenAlex
- W2439361170
- Cited by
- 152
- References
- 59
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 20 · 2023: 24 · 2022: 20 · 2021: 23 · 2020: 12 · 2019: 13 · 2018: 7 · 2017: 12 · 2016: 1
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Science Foundation (CHE-1531823)
- U.S. Department of Health and Human Services (P01HL112761, R01HL089221)
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- adeno-associated virus, charge detection mass spectrometry, empty capsids, self-complementary AAV, genome packaging, gene therapy vectors
- MeSH terms
- Dependovirus, Capsid, DNA, Viral, Genetic Vectors, Microscopy, Electron, Mass Spectrometry, Capsid Proteins
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