ArticleCytotherapy2013
Optimizing the transduction efficiency of capsid-modified AAV6 serotype vectors in primary human hematopoietic stem cells in vitro and in a xenograft mouse model in vivo.
Article in Cytotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 79 citations in OpenAlex.
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- ATM Inhibition Enhances Knock-in Efficiency by Suppressing AAV-Induced Activation of Apoptotic Pathways.Communications biology · 2026Article
- Have we really solved rAAV6 toxicity? A closer look at mannose-coupled rAAV6 vectors.Molecular therapy. Nucleic acids · 2025Article
- Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Adeno-Associated Virus-Engineered Umbilical Cord-Derived Mesenchymal Stromal Cells Overexpressing Human sFlt-1 for Anti-Angiogenesis.Life (Basel, Switzerland) · 2025Article
- AAV vector transduction restriction and attenuated toxicity in hESCs via a rationally designed inverted terminal repeat.Nucleic acids research · 2025Article
- Enhanced transgene expression from single-stranded AAV vectors in human cellsMolecular therapy. Nucleic acids · 2024Article
- Article
- Rationale and strategies for the development of safe and effective optimized AAV vectors for human gene therapy.Molecular therapy. Nucleic acids · 2023Review
- Review
- Fantastic AAV Gene Therapy Vectors and How to Find Them-Random Diversification, Rational Design and Machine Learning.Pathogens (Basel, Switzerland) · 2022Review
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- A precise gene delivery approach for human induced pluripotent stem cells using Cas9 RNP complex and recombinant AAV6 donor vectors.PloS one · 2022Article
- Genome Editing With TALEN, CRISPR-Cas9 and CRISPR-Cas12a in Combination With AAV6 Homology Donor Restores T Cell Function for XLP.Frontiers in genome editing · 2022Article
- Optimization of AAV6 transduction enhances site-specific genome editing of primary human lymphocytes.Molecular therapy. Methods & clinical development · 2021Article
- 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
- Harnessing the Natural Biology of Adeno-Associated Virus to Enhance the Efficacy of Cancer Gene Therapy.Viruses · 2021Review
- 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
- CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021Review
Corrections and comments
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Authors and funding
21 authors at 8 institutions in 3 countries.
Funding
Abstract
BACKGROUND
aimsAlthough recombinant adeno-associated virus serotype 2 (AAV2) vectors have gained attention because of their safety and efficacy in numerous phase I/II clinical trials, their transduction efficiency in hematopoietic stem cells (HSCs) has been reported to be low. Only a few additional AAV serotype vectors have been evaluated, and comparative analyses of their transduction efficiency in HSCs from different species have not been performed.
methodsWe evaluated the transduction efficiency of all available AAV serotype vectors (AAV1 through AAV10) in primary mouse, cynomolgus monkey and human HSCs. The transduction efficiency of the optimized AAV vectors was also evaluated in human HSCs in a murine xenograft model in vivo.
resultsWe observed that although there are only six amino acid differences between AAV1 and AAV6, AAV1, but not AAV6, transduced mouse HSCs well, whereas AAV6, but not AAV1, transduced human HSCs well. None of the 10 serotypes transduced cynomolgus monkey HSCs in vitro. We also evaluated the transduction efficiency of AAV6 vectors containing mutations in surface-exposed tyrosine residues. We observed that tyrosine (Y) to phenylalanine (F) point mutations in residues 445, 705 and 731 led to a significant increase in transgene expression in human HSCs in vitro and in a mouse xenograft model in vivo.
conclusionsThese studies suggest that the tyrosine-mutant AAV6 serotype vectors are the most promising vectors for transducing human HSCs and that it is possible to increase further the transduction efficiency of these vectors for their potential use in HSC-based gene therapy in humans.
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