ArticleMolecular therapy. Methods & clinical development2022
Analysis of thermally driven structural changes, genome release, disassembly, and aggregation of recombinant AAV by CDMS.
Article in Molecular therapy. Methods & clinical development, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Critical evaluation of the impact of ssDNA cargo length on AAV stability - a case study.Pharmaceutical research · 2026Article
- Accurate Sizing and Resolution of Nominal 200 nm Diameter Polystyrene Nanospheres With Charge Detection Mass Spectrometry.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Imaged Capillary Isoelectric Focusing (icIEF) Platform for Characterization of Charge Variants of Adeno-Associated Virus (AAV) Capsids and Impact on their Transduction Efficiency.Current gene therapy · 2026Article
- Quantifying the Full-to-Empty Adeno-Associated Virus (AAV) Capsid Ratios and Their Impact on Transduction Efficiency in vitro.The AAPS journal · 2025Article
- Adeno-associated virus serotype 9 structural heterogeneity and stability characterized by charge detection mass spectrometry.Molecular therapy. Methods & clinical development · 2025Article
- HDX-MS reveals pH and temperature-responsive regions on AAV capsids and the structural basis for DNA release.Gene therapy · 2025Article
- An Online Buffer Exchange Platform for Charge Detection Mass Spectrometry Analysis of AAVs and AAV-Antibody Complexes.Journal of the American Society for Mass Spectrometry · 2025Article
- Single particle charge detection mass spectrometry enables molecular characterization of lipid nanoparticles and mRNA packaging.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Unfolding of viral protein 1 N-termini facilitates genome ejection from recombinant adeno-associated virus serotype 8.Molecular therapy. Methods & clinical development · 2025Article
- A Robust and Automated Platform for Charge Detection Mass Spectrometry of Megadalton Biotherapeutics.Analytical chemistry · 2025Article
- Physicochemical and biological impacts of light stress on adeno-associated virus serotype 6.Molecular therapy. Methods & clinical development · 2024Article
- Probing recombinant AAV capsid integrity and genome release after thermal stress by mass photometry.Molecular therapy. Methods & clinical development · 2024Article
- Resolving hidden subpopulations of filled AAVs by probing capsid integrity.Molecular therapy. Methods & clinical development · 2024Article
- Charge Detection Mass Spectrometry Enables Molecular Characterization of Nucleic Acid Nanoparticles.ACS nano · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- An Online Native Mass Spectrometry Approach for Fast, Sensitive, and Quantitative Assessment of Adeno-Associated Virus Capsid Content Ratios.Journal of the American Society for Mass Spectrometry · 2024Article
- Analytical characterization of full, intermediate, and empty AAV capsids.Gene therapy · 2024Article
- Analysis of the impact of pluronic acid on the thermal stability and infectivity of AAV6.2FF.BMC biotechnology · 2024Article
- Single-Ion Mass Spectrometry for Heterogeneous and High Molecular Weight Samples.Journal of the American Chemical Society · 2024Review
- Multiple Ion Charge Extraction (MICE) for High-Throughput Charge Detection Mass Spectrometry.Analytical chemistry · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charge detection mass spectrometry (CDMS) was used to analyze recombinant adeno-associated virus serotype 8 (rAAV8) vectors after incubation at elevated temperatures. rAAV8 vectors with a range of genomes of interest (GOIs) from 2.22 to 4.84 kb were investigated. For the shorter GOIs, GOI release occurred at surprisingly low temperatures (15 min at 45°C for cytomegalovirus [CMV]-GFP). The released DNA and intermediates with the GOI extruded from the capsid were detected. The temperature required to release the short GOIs is well below the 65°C incubation temperature required to disassemble the empty rAAV8 capsid. The temperature for GOI release increased with its GOI length. With the longer GOIs, the GOI stabilized the capsid so that it remained intact under conditions that would disassemble the empty particle. After incubation at 65°C, the main species in the CDMS mass distributions for the longer GOIs was the vector with the GOI. However, for GOIs longer than the wild-type genome (∼4.7 kb), the stability diminished, and genome release occurred at a lower temperature. Heterogeneous DNA fragments from the host cells or plasmids is released at a lower temperature than the longer GOIs, suggesting that the GOIs have a feature that resists early release.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.