ArticlePloS one2013
High-efficiency transduction of primary human hematopoietic stem cells and erythroid lineage-restricted expression by optimized AAV6 serotype vectors in vitro and in a murine xenograft model in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Review
- Ligand-modified rAAV6 vectors with nanoblades allow high-level gene knockin in HSPCs without compromising cell survival.Molecular therapy. Nucleic acids · 2025Article
- Enhanced transgene expression from single-stranded AAV vectors in human cellsMolecular therapy. Nucleic acids · 2024Article
- Rationale and strategies for the development of safe and effective optimized AAV vectors for human gene therapy.Molecular therapy. Nucleic acids · 2023Review
- Nanoparticles targeting hematopoietic stem and progenitor cells: Multimodal carriers for the treatment of hematological diseases.Frontiers in genome editing · 2022Review
- Optimization of AAV6 transduction enhances site-specific genome editing of primary human lymphocytes.Molecular therapy. Methods & clinical development · 2021Article
- Correction of X-CGD patient HSPCs by targeted CYBB cDNA insertion using CRISPR/Cas9 with 53BP1 inhibition for enhanced homology-directed repair.Gene therapy · 2021Article
- Can early treatment of twitcher mice with high dose AAVrh10-GALC eliminate the need for BMT?BioImpacts : BI · 2021Article
- Adeno-Associated Virus Vector Mobilization, Risk Versus Reality.Human gene therapy · 2020Article
- Ocular Tolerability and Immune Response to Corneal Intrastromal AAV-Molecular therapy. Methods & clinical development · 2020Article
- Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.Molecular therapy. Nucleic acids · 2020Article
- Cyclosporine H Improves the Multi-Vector Lentiviral Transduction of Murine Haematopoietic Progenitors and Stem Cells.Scientific reports · 2020Article
- Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions.Journal of hematology & oncology · 2019Review
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- Gene Delivery to Human Limbal Stem Cells Using Viral Vectors.Human gene therapy · 2019Article
- Internal Ribosome Entry Site Dramatically Reduces Transgene Expression in Hematopoietic Cells in a Position-Dependent Manner.Viruses · 2019Article
- Editing the Sickle Cell Disease Mutation in Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Serotype survey of AAV gene delivery via subconjunctival injection in mice.Gene therapy · 2018Article
- CRISPR/Cas9 genome editing in human hematopoietic stem cells.Nature protocols · 2018Article
- A directed evolution approach to select for novel Adeno-associated virus capsids on an HIV-1 producer T cell line.Journal of virological methods · 2017Article
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
Abstract
We have observed that of the 10 AAV serotypes, AAV6 is the most efficient in transducing primary human hematopoietic stem cells (HSCs), and that the transduction efficiency can be further increased by specifically mutating single surface-exposed tyrosine (Y) residues on AAV6 capsids. In the present studies, we combined the two mutations to generate a tyrosine double-mutant (Y705+731F) AAV6 vector, with which >70% of CD34(+) cells could be transduced. With the long-term objective of developing recombinant AAV vectors for the potential gene therapy of human hemoglobinopathies, we generated the wild-type (WT) and tyrosine-mutant AAV6 vectors containing the following erythroid cell-specific promoters: β-globin promoter (βp) with the upstream hyper-sensitive site 2 (HS2) enhancer from the β-globin locus control region (HS2-βbp), and the human parvovirus B19 promoter at map unit 6 (B19p6). Transgene expression from the B19p6 was significantly higher than that from the HS2-βp, and increased up to 30-fold and up to 20-fold, respectively, following erythropoietin (Epo)-induced differentiation of CD34(+) cells in vitro. Transgene expression from the B19p6 or the HS2-βp was also evaluated in an immuno-deficient xenograft mouse model in vivo. Whereas low levels of expression were detected from the B19p6 in the WT AAV6 capsid, and that from the HS2-βp in the Y705+731F AAV6 capsid, transgene expression from the B19p6 promoter in the Y705+731F AAV6 capsid was significantly higher than that from the HS2-βp, and was detectable up to 12 weeks post-transplantation in primary recipients, and up to 6 additional weeks in secondary transplanted animals. These data demonstrate the feasibility of the use of the novel Y705+731F AAV6-B19p6 vectors for high-efficiency transduction of HSCs as well as expression of the b-globin gene in erythroid progenitor cells for the potential gene therapy of human hemoglobinopathies such as β-thalassemia and sickle cell disease.
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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.