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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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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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