ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Deamidation of Amino Acids on the Surface of Adeno-Associated Virus Capsids Leads to Charge Heterogeneity and Altered Vector Function.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
59 citing papers in PubMed, 118 citations in OpenAlex.
- Anion-exchange chromatography separates structurally heterogeneous and low-potency particles in adeno-associated virus manufacture.Molecular therapy. Advances · 2026Article
- Immunogenicity in Approved Adeno-Associated Virus-Based Gene Therapies: A Framework for a Tailored Assessment Strategy.The AAPS journal · 2026Review
- Critical evaluation of the impact of ssDNA cargo length on AAV stability - a case study.Pharmaceutical research · 2026Article
- Comprehensive forced degradation study revealing diverse chemical and physical degradation pathways of AAV8.Gene therapy · 2026Article
- Manufacture of adeno-associated virus vectors by a novel human-derived cell line HAT and comprehensive evaluation of the vectors.Molecular therapy. Advances · 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
- Variation of VP2 stoichiometry and deamidation of VP1 during production and their impacts on the transduction efficiency of AAV vectors.Molecular therapy. Methods & clinical development · 2025Article
- pH-dependent DNA degradation pathways for adeno-associated virus gene therapy.Molecular therapy. Methods & clinical development · 2025Article
- Development and implementation of an LC-MS-based multi-attribute method for adeno-associated virus.Molecular therapy. Methods & clinical development · 2025Article
- Development of LC-MS methods for AAV capsid protein quantification and host cell protein profiling.Molecular therapy. Methods & clinical development · 2025Article
- A single amino acid variant in the variable region I of AAV capsid confers liver detargeting.PLoS pathogens · 2025Article
- Insights into Adeno-Associated Virus Capsid Charge Heterogeneity.Analytical chemistry · 2025Article
- A clinician's guide to AAV production - How manufacturing platforms shape vector properties.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- A two-pass anion-exchange chromatography strategy for enrichment of full capsids in manufacturing of adeno-associated viral vectors.Molecular therapy. Methods & clinical development · 2025Article
- Advances in the Study of Protein Deamidation: Unveiling Its Influence on Aging, Disease Progression, Forensics and Therapeutic Efficacy.Proteomes · 2025Review
- Combination of hydrophilic interaction liquid chromatography and top-down mass spectrometry for characterisation of adeno-associated virus capsid proteins.Analytical and bioanalytical chemistry · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Chromatography in Downstream Processing of Recombinant Adeno-Associated Viruses: A Review of Current and Future Practises.Biotechnology and bioengineering · 2025Review
- A Review on the Stability Challenges of Advanced Biologic Therapeutics.Pharmaceutics · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Post-translational modification of the adeno-associated virus capsids is a poorly understood factor in the development of these viral vectors into pharmaceutical products. Here we report the extensive capsid deamidation of adeno-associated virus serotype 8 and seven other diverse adeno-associated virus serotypes, with supporting evidence from structural, biochemical, and mass spectrometry approaches. The extent of deamidation at each site depended on the vector's age and multiple primary-sequence and three-dimensional structural factors. However, the extent of deamidation was largely independent of the vector recovery and purification conditions. We demonstrate the potential for deamidation to impact transduction activity and, moreover, correlate an early time point loss in vector activity to rapidly progressing spontaneous deamidation at several adeno-associated virus 8 asparagines. We explore mutational strategies that stabilize side-chain amides, improving vector transduction and reducing the lot-to-lot molecular variability that presents a key concern in biologics manufacturing. This study illuminates a previously unknown aspect of adeno-associated virus capsid heterogeneity and highlights its importance in the development of these vectors for gene therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.