ArticleJournal of virology2013
Biophysical and ultrastructural characterization of adeno-associated virus capsid uncoating and genome release.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
81 citing papers in PubMed.
- DNA ejection and AAV capsid degradation under thermal stress: Insights from CDMS and native digestion strategies.Molecular therapy. Advances · 2026Article
- Critical evaluation of the impact of ssDNA cargo length on AAV stability - a case study.Pharmaceutical research · 2026Article
- An Automated Workflow Leveraging Machine Learning for Physical Titer Determination from Cryo-TEM Images of Adeno-Associated Virus Capsids.Chemical & biomedical imaging · 2026Article
- Renovating Neural Networks With Viral-Mediated Gene Transfer From A Tissue Contacting Matrix Mimic.Small (Weinheim an der Bergstrasse, Germany) · 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
- pH-dependent DNA degradation pathways for adeno-associated virus gene therapy.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
- Identification of relevant analytical methods for adeno-associated virus stability assessment during formulation development.Microbiology spectrum · 2025Article
- Real-time genome imaging of host interactions in adeno-associated virus genome release.iScience · 2025Article
- Unfolding of viral protein 1 N-termini facilitates genome ejection from recombinant adeno-associated virus serotype 8.Molecular therapy. Methods & clinical development · 2025Article
- Biophysical and structural insights into AAV genome ejection.Journal of virology · 2025Article
- A novel platform for engineered AAV-based vaccines.Molecular therapy. Methods & clinical development · 2025Article
- Size-exclusion chromatography as a multi-attribute method for process and product characterization of adeno-associated virus.Molecular therapy. Methods & clinical development · 2024Article
- Physicochemical and biological impacts of light stress on adeno-associated virus serotype 6.Molecular therapy. Methods & clinical development · 2024Article
- Development of an optimized SEC method for characterization of genome DNA leakage from adeno-associated virus products.Analytical and bioanalytical chemistry · 2024Article
- A Spatial Interpolation Approach to Assign Magnetic Resonance Imaging-Derived Material Properties for Finite Element Models of Adeno-Associated Virus Infusion Into a Recurrent Brain Tumor.Journal of biomechanical engineering · 2024Article
- Probing recombinant AAV capsid integrity and genome release after thermal stress by mass photometry.Molecular therapy. Methods & clinical development · 2024Article
- The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2.Gene therapy · 2024Article
- Sendai virus-mediated RNA delivery restores fertility to congenital and chemotherapy-induced infertile female mice.PNAS nexus · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
We describe biophysical and ultrastructural differences in genome release from adeno-associated virus (AAV) capsids packaging wild-type DNA, recombinant single-stranded DNA (ssDNA), or dimeric, self-complementary DNA (scDNA) genomes. Atomic force microscopy and electron microscopy (EM) revealed that AAV particles release packaged genomes and undergo marked changes in capsid morphology upon heating in physiological buffer (pH 7.2). When different AAV capsids packaging ss/scDNA varying in length from 72 to 123% of wild-type DNA (3.4 to 5.8 kb) were incrementally heated, the proportion of uncoated AAV capsids decreased with genome length as observed by EM. Genome release was further characterized by a fluorimetric assay, which demonstrated that acidic pH and high osmotic pressure suppress genome release from AAV particles. In addition, fluorimetric analysis corroborated an inverse correlation between packaged genome length and the temperature needed to induce uncoating. Surprisingly, scAAV vectors required significantly higher temperatures to uncoat than their ssDNA-packaging counterparts. However, externalization of VP1 N termini appears to be unaffected by packaged genome length or self-complementarity. Further analysis by tungsten-shadowing EM revealed striking differences in the morphologies of ssDNA and scDNA genomes upon release from intact capsids. Computational modeling and molecular dynamics simulations suggest that the unusual thermal stability of scAAV vectors might arise from partial base pairing and optimal organization of packaged scDNA. Our work further defines the biophysical mechanisms underlying adeno-associated virus uncoating and genome release.
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