ArticlePloS one2022
Assessment of the percentage of full recombinant adeno-associated virus particles in a gene therapy drug using CryoTEM.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 24 citations in OpenAlex.
- An Automated Workflow Leveraging Machine Learning for Physical Titer Determination from Cryo-TEM Images of Adeno-Associated Virus Capsids.Chemical & biomedical imaging · 2026Article
- Methodological validation of a cryo-TEM-based detection method for empty capsid ratio in recombinant adeno-associated virus.Biochemistry and biophysics reports · 2026Article
- Orthogonal approaches to AAV vector characterization: Validating quantitative TEM for partially filled particles.Molecular therapy. Methods & clinical development · 2025Article
- Preclinical development of TAK-754, a high-performance AAV8-based vector expressing coagulation factor VIII.Molecular therapy. Methods & clinical development · 2025Article
- Crucial aspects for maintaining rAAV stability.Scientific reports · 2024Article
- In-Depth Comparison of Adeno-Associated Virus Containing Fractions after CsCl Ultracentrifugation Gradient Separation.Viruses · 2024Article
- Hybrid modeling of an ultracentrifugation process for separation of full and empty adeno-associated virus particles.Bioprocess and biosystems engineering · 2024Article
- Applications and Limitations of Equilibrium Density Gradient Analytical Ultracentrifugation for the Quantitative Characterization of Adeno-Associated Virus Vectors.Analytical chemistry · 2024Article
- Characterization and quantification of adeno-associated virus capsid-loading states by multi-wavelength analytical ultracentrifugation with UltraScan.Nanomedicine (London, England) · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In spite of continuous development of gene therapy vectors with thousands of drug candidates in clinical drug trials there are only a small number approved on the market today stressing the need to have characterization methods to assist in the validation of the drug development process. The level of packaging of the vector capsids appears to play a critical role in immunogenicity, hence an objective quantitative method assessing the content of particles containing a genome is an essential quality measurement. As transmission electron microscopy (TEM) allows direct visualization of the particles present in a specimen, it naturally seems as the most intuitive method of choice for characterizing recombinant adeno-associated virus (rAAV) particle packaging. Negative stain TEM (nsTEM) is an established characterization method for analysing the packaging of viral vectors. It has however shown limitations in terms of reliability. To overcome this drawback, we propose an analytical method based on CryoTEM that unambiguously and robustly determines the percentage of filled particles in an rAAV sample. In addition, we show that at a fixed number of vector particles the portion of filled particles correlates well with the potency of the drug. The method has been validated according to the ICH Q2 (R1) guidelines and the components investigated during the validation are presented in this study. The reliability of nsTEM as a method for the assessment of filled particles is also investigated along with a discussion about the origin of the observed variability of this method.
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