ArticleHuman gene therapy2010
High-efficiency transduction of fibroblasts and mesenchymal stem cells by tyrosine-mutant AAV2 vectors for their potential use in cellular therapy.
Article in Human gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed, 67 citations in OpenAlex.
- CRISPR and Gene Augmentation Rescue Trabecular Meshwork Dysfunction in iPSC Models of Lowe Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery.Nature communications · 2022Article
- Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications.Gene therapy · 2021Article
- Conditioned medium derived from bovine umbilical mesenchymal stem cells as an alternative source of cell-free therapy.Veterinary world · 2021Review
- AAV3-miRNA vectors for growth suppression of human hepatocellular carcinoma cells in vitro and human liver tumors in a murine xenograft model in vivo.Gene therapy · 2021Article
- Site-specific modifications to AAV8 capsid yields enhanced brain transduction in the neonatal MPS IIIB mouse.Gene therapy · 2021Article
- Tissue and cell-type-specific transduction using rAAV vectors in lung diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Effects of Altering HSPG Binding and Capsid Hydrophilicity on Retinal Transduction by AAV.Journal of virology · 2021Article
- AAV vectors engineered to target insulin receptor greatly enhance intramuscular gene delivery.Molecular therapy. Methods & clinical development · 2020Article
- Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants.Nature communications · 2020Article
- Compromised DNA repair is responsible for diabetes-associated fibrosis.The EMBO journal · 2020Article
- Increased mtDNA Abundance and Improved Function in Human Barth Syndrome Patient Fibroblasts Following AAV-International journal of molecular sciences · 2019Article
- Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System.Medicines (Basel, Switzerland) · 2018Review
- Gene Delivery Approaches for Mesenchymal Stem Cell Therapy: Strategies to Increase Efficiency and Specificity.Stem cell reviews and reports · 2017Review
- Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases.Heart failure reviews · 2017Review
- Rationally Engineered AAV Capsids Improve Transduction and Volumetric Spread in the CNS.Molecular therapy. Nucleic acids · 2017Article
- Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?Human gene therapy · 2017Review
- Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Adeno-associated Virus Vectors Efficiently Transduce Mouse and Rabbit Sensory Neurons Coinfected with Herpes Simplex Virus 1 following Peripheral Inoculation.Journal of virology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Adeno-associated virus 2 (AAV2) vectors transduce fibroblasts and mesenchymal stem cells (MSCs) inefficiently, which limits their potential widespread applicability in combinatorial gene and cell therapy. We have reported that AAV2 vectors fail to traffic efficiently to the nucleus in murine fibroblasts. We have also reported that site-directed mutagenesis of surface-exposed tyrosine residues on viral capsids leads to improved intracellular trafficking of the mutant vectors, and the transduction efficiency of the single tyrosine-mutant vectors is ∼10-fold higher in human cells. In the current studies, we evaluated the transduction efficiency of single as well as multiple tyrosine-mutant AAV2 vectors in murine fibroblasts. Our results indicate that the Y444F mutant vectors transduce these cells most efficiently among the seven single-mutant vectors, with >30-fold increase in transgene expression compared with the wild-type vectors. When the Y444F mutation is combined with additional mutations (Y500F and Y730F), the transduction efficiency of the triple-mutant vectors is increased by ∼130-fold and the viral intracellular trafficking is also significant improved. Similarly, the triple-mutant vectors are capable of transducing up to 80-90% of bone marrow-derived primary murine as well as human MSCs. Thus, high-efficiency transduction of fibroblasts with reprogramming genes to generate induced pluripotent stem cells, and the MSCs for delivering therapeutic genes, should now be feasible with the tyrosine-mutant AAV vectors.
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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.