ArticleVirology2008
Tyrosine-phosphorylation of AAV2 vectors and its consequences on viral intracellular trafficking and transgene expression.
Article in Virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 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
161 citing papers in PubMed, 223 citations in OpenAlex.
- Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.JAMA ophthalmology · 2014Trial
- Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- Review
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Suppressing microtubule detyrosination augments adeno-associated virus 2 endosomal escape and gene delivery.Journal of cell science · 2025Article
- Review
- Adeno-Associated Virus 2 (AAV2) - Induced RPA exhaustion generates cellular DNA damage and restricts viral gene expression.PLoS pathogens · 2025Article
- Real-time genome imaging of host interactions in adeno-associated virus genome release.iScience · 2025Article
- Adeno-associated viral vector targeted evolution for neurofibromatosis gene delivery.Trends in molecular medicine · 2025Review
- Cell-penetrating peptide-grafted AAV2 capsids for improved retinal delivery via intravitreal injection.Molecular therapy. Methods & clinical development · 2025Article
- Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases.International journal of molecular sciences · 2025Review
- The role of post-translational modifications in parvovirus life cycle.Frontiers in veterinary science · 2025Review
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Recombinant adeno-associated virus as a delivery platform for ocular gene therapy: A comprehensive review.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Article
- Characterization of AAV vectors: A review of analytical techniques and critical quality attributes.Molecular therapy. Methods & clinical development · 2024Review
- Engineered AAV13 variants with enhanced transduction and confined spread.Zoological research · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Innate Immune Sensing of Adeno-Associated Virus Vectors.Human gene therapy · 2024Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
We have documented that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects intracellular trafficking and transduction efficiency of recombinant adeno-associated virus 2 (AAV2) vectors. Specifically, inhibition of EGFR-PTK signaling leads to decreased ubiquitination of AAV2 capsid proteins, which in turn, facilitates viral nuclear transport by limiting proteasome-mediated degradation of AAV2 vectors. In the present studies, we observed that AAV capsids can indeed be phosphorylated at tyrosine residues by EGFR-PTK in in vitro phosphorylation assays and that phosphorylated AAV capsids retain their structural integrity. However, although phosphorylated AAV vectors enter cells as efficiently as their unphosphorylated counterparts, their transduction efficiency is significantly reduced. This reduction is not due to impaired viral second-strand DNA synthesis since transduction efficiency of both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors is decreased by approximately 68% and approximately 74%, respectively. We also observed that intracellular trafficking of tyrosine-phosphorylated AAV vectors from cytoplasm to nucleus is significantly decreased, which results from ubiquitination of AAV capsids followed by proteasome-mediated degradation, although downstream consequences of capsid ubiquitination may also be affected by tyrosine-phosphorylation. These studies provide new insights into the role of tyrosine-phosphorylation of AAV capsids in various steps in the virus life cycle, which has implications in the optimal use of recombinant AAV vectors in human gene therapy.
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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.