ArticleHuman gene therapy2013
The nontoxic cell cycle modulator indirubin augments transduction of adeno-associated viral vectors and zinc-finger nuclease-mediated gene targeting.
Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- CRISPR/Cas9 Genome Editing in the Diamondback Moth: Current Progress, Challenges, and Prospects.International journal of molecular sciences · 2025Review
- Recent developments, challenges and opportunities in genome editing for crop science from a societal perspective.Frontiers in genome editing · 2025Review
- Recent advances in CRISPR-Cas9-based genome insertion technologies.Molecular therapy. Nucleic acids · 2024Review
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- Selecting for CRISPR-Edited Knock-In Cells.International journal of molecular sciences · 2022Review
- Improving Homology-Directed Repair in Genome Editing Experiments by Influencing the Cell Cycle.International journal of molecular sciences · 2022Review
- Advance trends in targeting homology-directed repair for accurate gene editing: An inclusive review of small molecules and modified CRISPR-Cas9 systems.BioImpacts : BI · 2022Review
- The Problem of the Low Rates of CRISPR/Cas9-Mediated Knock-ins in Plants: Approaches and Solutions.International journal of molecular sciences · 2019Review
- Ways of improving precise knock-in by genome-editing technologies.Human genetics · 2019Review
- Optimization of a CRISPR/Cas9-mediated Knock-in Strategy at the Porcine Rosa26 Locus in Porcine Foetal Fibroblasts.Scientific reports · 2017Article
- Integration-defective lentiviral vector mediates efficient gene editing through homology-directed repair in human embryonic stem cells.Nucleic acids research · 2017Article
- In Vivo Delivery Systems for Therapeutic Genome Editing.International journal of molecular sciences · 2016Review
- Engineered Viruses as Genome Editing Devices.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Genome Engineering Using Adeno-associated Virus: Basic and Clinical Research Applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Targeted Integration of a Super-Exon into the CFTR Locus Leads to Functional Correction of a Cystic Fibrosis Cell Line Model.PloS one · 2016Article
- In vitro screening of clinical drugs identifies sensitizers of oncolytic viral therapy in glioblastoma stem-like cells.Gene therapy · 2015Article
- Adeno-associated Virus as a Mammalian DNA Vector.Microbiology spectrum · 2015Review
- Small molecules enhance CRISPR genome editing in pluripotent stem cells.Cell stem cell · 2015Article
- Adenoviral vector DNA for accurate genome editing with engineered nucleases.Nature methods · 2014Article
- Non-integrating gamma-retroviral vectors as a versatile tool for transient zinc-finger nuclease delivery.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parameters that regulate or affect the cell cycle or the DNA repair choice between non-homologous end-joining and homology-directed repair (HDR) are excellent targets to enhance therapeutic gene targeting. Here, we have evaluated the impact of five cell-cycle modulating drugs on targeted genome engineering mediated by DNA double-strand break (DSB)-inducing nucleases, such as zinc-finger nucleases (ZFNs). For a side-by-side comparison, we have established four reporter cell lines by integrating a mutated EGFP gene into either three transformed human cell lines or primary umbilical cord-derived mesenchymal stromal cells (UC-MSCs). After treatment with different cytostatic drugs, cells were transduced with adeno-associated virus (AAV) vectors that encode a nuclease or a repair donor to rescue EGFP expression through DSB-induced HDR. We show that transient cell-cycle arrest increased AAV transduction and AAV-mediated HDR up to six-fold in human cell lines and ten-fold in UC-MSCs, respectively. Targeted gene correction was observed in up to 34% of transduced cells. Both the absolute and the relative gene-targeting frequencies were dependent on the cell type, the cytostatic drug, the vector dose, and the nuclease. Treatment of cells with the cyclin-dependent kinase inhibitor indirubin-3'-monoxime was especially promising as this compound combined high stimulatory effects with minimal cytotoxicity. In conclusion, indirubin-3'-monoxime significantly improved AAV transduction and the efficiency of AAV/ZFN-mediated gene targeting and may thus represent a promising compound to enhance DSB-mediated genome engineering in human stem cells, such as UC-MSCs, which hold great promise for future clinical applications.
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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.