ArticleGene therapy2016
Development of novel AAV serotype 6 based vectors with selective tropism for human cancer cells.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Heterologous prime-boost immunization of AAV-based neoantigen cancer vaccine induces anti-tumor immunity to inhibit tumor growth and relapse.Cancer immunology, immunotherapy : CII · 2026Article
- AAV for ovarian cancer gene therapy.Cancer gene therapy · 2025Review
- Development of an Optimized Promoter System for Exosomal and Naked AAV Vector-Based Suicide Gene Therapy in Hepatocellular Carcinoma.ACS omega · 2024Article
- Inducible caspase 9-mediated suicide gene therapy using AAV6 vectors in a murine model of breast cancer.Molecular therapy. Methods & clinical development · 2023Article
- Chemical modification of AAV9 capsid with N-ethyl maleimide alters vector tissue tropism.Scientific reports · 2023Article
- Adding recombinant AAVs to the cancer therapeutics mix.Molecular therapy oncolytics · 2022Review
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review.Annals of translational medicine · 2022Review
- Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening.Scientific reports · 2022Article
- Vector engineering, strategies and targets in cancer gene therapy.Cancer gene therapy · 2022Review
- Intra-tracheal delivery of AAV6 vectors results in sustained transduction in murine lungs without genomic integration.Gene: X · 2020Article
- Modifiers of Adeno-Associated Virus-Mediated Gene Expression in Implication for Serotype-Universal Neutralizing Antibody Assay.Human gene therapy · 2020Article
- Review
- AAV6 Vexosomes Mediate Robust Suicide Gene Delivery in a Murine Model of Hepatocellular Carcinoma.Molecular therapy. Methods & clinical development · 2020Article
- Pre-arrayed Pan-AAV Peptide Display Libraries for Rapid Single-Round Screening.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Capsid Modifications for Targeting and Improving the Efficacy of AAV Vectors.Molecular therapy. Methods & clinical development · 2019Review
- An Adeno-Associated Viral Vector Capable of Penetrating the Mucus Barrier to Inhaled Gene Therapy.Molecular therapy. Methods & clinical development · 2018Article
- A novel and highly efficient AAV6 mutant.Virus genes · 2018Article
- Extraction ofEvidence-based complementary and alternative medicine : eCAM · 2018Article
- Emerging Gene Therapies for Genetic Hearing Loss.Journal of the Association for Research in Otolaryngology : JARO · 2017Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viral vectors-based gene therapy is an attractive alternative to common anti-cancer treatments. In the present studies, AAV serotype 6 vectors were identified to be particularly effective in the transduction of human prostate (PC3), breast (T47D) and liver (Huh7) cancer cells. Next, we developed chimeric AAV vectors with Arg-Gly-Asp (RGD) peptide incorporated into the viral capsid to enable specific targeting of integrin-overexpressing malignant cells. These AAV6-RGD vectors improved transduction efficiency approximately 3-fold compared with wild-type AAV6 vectors by enhancing the viral entry into the cells. We also observed that transduction efficiency significantly improved, up to approximately 5-fold, by the mutagenesis of surface-exposed tyrosine and threonine residues involved in the intracellular trafficking of AAV vectors. Therefore, in our study, the AAV6-Y705-731F+T492V vector was identified as the most efficient. The combination of RGD peptide, tyrosine and threonine mutations on the same AAV6 capsid further increased the transduction efficiency, approximately 8-fold in vitro. In addition, we mutated lysine (K531E) to impair the affinity of AAV6 vectors to heparan sulfate proteoglycan. Finally, we showed a significant increase in both specificity and efficiency of AAV6-RGD-Y705-731F+T492V+K531E vectors in a xenograft animal model in vivo. In summary, the approach described here can lead to the development of AAV vectors with selective tropism to human cancer 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.