ArticleJournal of virology2017
Relevance of Assembly-Activating Protein for Adeno-associated Virus Vector Production and Capsid Protein Stability in Mammalian and Insect Cells.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- A clinician's guide to AAV production - How manufacturing platforms shape vector properties.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Perfusion-Based Production of rAAV via an Intensified Transient Transfection Process.Biotechnology and bioengineering · 2025Article
- Improved Recombinant Adeno-Associated Viral Vector Production via Molecular Evolution of the Viral Rep Protein.International journal of molecular sciences · 2025Article
- Adeno-Associated Viral Vectors in the Treatment of Epilepsy.International journal of molecular sciences · 2024Review
- The Expression and Function of the Small Nonstructural Proteins of Adeno-Associated Viruses (AAVs).Viruses · 2024Review
- Role of the membrane-associated accessory protein (MAAP) in adeno-associated virus (AAV) infection.Journal of virology · 2024Article
- Evolving membrane-associated accessory protein variants for improved adeno-associated virus production.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Assembly of Structurally Simple Icosahedral Viruses.Sub-cellular biochemistry · 2024Review
- Gene therapy of adeno-associated virus (AAV) vectors in preclinical models of ischemic stroke.CNS neuroscience & therapeutics · 2023Review
- Mechanistic modeling explains the production dynamics of recombinant adeno-associated virus with the baculovirus expression vector system.Molecular therapy. Methods & clinical development · 2023Article
- AAV genome modification for efficient AAV production.Heliyon · 2023Review
- Ex vivo and in vivo suppression of SARS-CoV-2 with combinatorial AAV/RNAi expression vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Mechanistic model for production of recombinant adeno-associated virus via triple transfection of HEK293 cells.Molecular therapy. Methods & clinical development · 2021Article
- Article
- Adeno-associated Virus (AAV) Capsid Chimeras with Enhanced Infectivity Reveal a Core Element in the AAV Genome Critical for both Cell Transduction and Capsid Assembly.Journal of virology · 2021Article
- Cross-Packaging and Capsid Mosaic Formation in Multiplexed AAV Libraries.Molecular therapy. Methods & clinical development · 2020Article
- Impact of Natural or Synthetic Singletons in the Capsid of Human Bocavirus 1 on Particle Infectivity and Immunoreactivity.Journal of virology · 2020Article
- Adeno-Associated Virus Genome Interactions Important for Vector Production and Transduction.Human gene therapy · 2020Review
- Article
- Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The discovery that adeno-associated virus 2 (AAV2) encodes an eighth protein, called assembly-activating protein (AAP), transformed our understanding of wild-type AAV biology. Concurrently, it raised questions about the role of AAP during production of recombinant vectors based on natural or molecularly engineered AAV capsids. Here, we show that AAP is indeed essential for generation of functional recombinant AAV2 vectors in both mammalian and insect cell-based vector production systems. Surprisingly, we observed that AAV2 capsid proteins VP1 to -3 are unstable in the absence of AAP2, likely due to rapid proteasomal degradation. Inhibition of the proteasome led to an increase of intracellular VP1 to -3 but neither triggered assembly of functional capsids nor promoted nuclear localization of the capsid proteins. Together, this underscores the crucial and unique role of AAP in the AAV life cycle, where it rapidly chaperones capsid assembly, thus preventing degradation of free capsid proteins. An expanded analysis comprising nine alternative AAV serotypes (1, 3 to 9, and rh10) showed that vector production always depends on the presence of AAP, with the exceptions of AAV4 and AAV5, which exhibited AAP-independent, albeit low-level, particle assembly. Interestingly, AAPs from all 10 serotypes could cross-complement AAP-depleted helper plasmids during vector production, despite there being distinct intracellular AAP localization patterns. These were most pronounced for AAP4 and AAP5, congruent with their inability to rescue an AAV2/AAP2 knockout. We conclude that AAP is key for assembly of genuine capsids from at least 10 different AAV serotypes, which has implications for vectors derived from wild-type or synthetic AAV capsids.
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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 Socratic graph.