ArticleHuman gene therapy2010
Enhanced long-term transduction and multilineage engraftment of human hematopoietic stem cells transduced with tyrosine-modified recombinant adeno-associated virus serotype 2.
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 22 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
22 citing papers in PubMed, 30 citations in OpenAlex.
- Understanding and overcoming adverse consequences of genome editing on hematopoietic stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Tissue and cell-type-specific transduction using rAAV vectors in lung diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.Molecular therapy. Nucleic acids · 2020Article
- Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines.Human gene therapy · 2020Review
- Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases.Heart failure reviews · 2017Review
- Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes?Human gene therapy · 2017Review
- Efficient Gene Delivery and Expression in Pancreas and Pancreatic Tumors by Capsid-Optimized AAV8 Vectors.Human gene therapy methods · 2017Article
- High-Efficiency Transduction of Primary Human Hematopoietic Stem/Progenitor Cells by AAV6 Vectors: Strategies for Overcoming Donor-Variation and Implications in Genome Editing.Scientific reports · 2016Article
- Single point mutation in adeno-associated viral vectors -DJ capsid leads to improvement for gene delivery in vivo.BMC biotechnology · 2016Article
- Improving clinical efficacy of adeno associated vectors by rational capsid bioengineering.Journal of biomedical science · 2014Review
- Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.Gene therapy · 2014Article
- Gene transfer properties and structural modeling of human stem cell-derived AAV.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Article
- Bioengineering of AAV2 capsid at specific serine, threonine, or lysine residues improves its transduction efficiency in vitro and in vivo.Human gene therapy methods · 2013Article
- Article
- Limitations of encapsidation of recombinant self-complementary adeno-associated viral genomes in different serotype capsids and their quantitation.Human gene therapy methods · 2012Article
- Intracellular transport of recombinant adeno-associated virus vectors.Gene therapy · 2012Review
- Single tyrosine mutation in AAV8 and AAV9 capsids is insufficient to enhance gene delivery to skeletal muscle and heart.Human gene therapy methods · 2012Article
- AAV vectors for cardiac gene transfer: experimental tools and clinical opportunities.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Review
- Quantifying transduction efficiencies of unmodified and tyrosine capsid mutant AAV vectors in vitro using two ocular cell lines.Molecular vision · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The search for the ideal stem cell gene therapy vector continues as recognized problems persist. Although recombinant adeno-associated virus serotype 2 (rAAV2) mediates gene transfer into hematopoietic stem cells, identified restrictions to transgene expression reduce overall efficiency. Studies have shown that transduction efficiencies are significantly improved by preventing early proteasomal degradation after mutation of surface-exposed tyrosine residues on the capsid to phenylalanine. Here, we report that transduction of human cord blood CD34(+) stem cells by tyrosine-modified rAAV2 is significantly enhanced both in vitro and in vivo. Serial long-term in vivo bioluminescent imaging of immune-deficient recipients after xenotransplantation of CD34(+) cells transduced with tyrosine-modified rAAV2-luciferase revealed that modification of rAAV2 capsids led to a significant increase in the transduction of human CD34(+) cells, without adversely affecting engraftment capacity, or the ability to undergo multilineage differentiation and self-renewal. Together with observations of sustained high-level transgene expression in vivo and efficient persistence of rAAV genomes in human hematopoietic cells, these results suggest that, because of their ability to bypass restrictions to transduction, tyrosine-modified rAAV vectors, particularly Y500F, Y700F, Y444F, and Y704F, represent highly promising candidates for therapeutic evaluation for diseases of human hematopoietic stem cells.
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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.