ArticleGene therapy2013
Chromatin structure of two genomic sites for targeted transgene integration in induced pluripotent stem cells and hematopoietic stem cells.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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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
32 citing papers in PubMed, 46 citations in OpenAlex.
- CRISPR/nCas9-Edited CD34+ Cells Rescue Mucopolysaccharidosis IVA Fibroblasts Phenotype.International journal of molecular sciences · 2025Article
- CutIn: a ready-to-use construct for rapid generation of urgently needed transgenic cell lines in emerging infection research.Functional & integrative genomics · 2025Article
- Auto-expansion ofMolecular therapy. Methods & clinical development · 2024Article
- An induced pluripotent stem cell line carrying a silencing-resistant calcium reporter allele.Stem cell research · 2024Article
- Overcoming the Silencing of Doxycycline-Inducible Promoters in hiPSC-derived Cardiomyocytes.Open research Europe · 2024Article
- Modern Approaches to Mouse Genome Editing Using the CRISPR-Cas Toolbox and Their Applications in Functional Genomics and Translational Research.Advances in experimental medicine and biology · 2023Review
- Validation of reliable safe harbor locus for efficient porcine transgenesis.Functional & integrative genomics · 2022Article
- Establishment and characterization of a novel human induced pluripotent stem cell line stably expressing the iRFP720 reporter.Scientific reports · 2022Article
- CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.Molecular therapy. Methods & clinical development · 2020Article
- TALEN mediated gene editing in a mouse model of Fanconi anemia.Scientific reports · 2020Article
- Targeted Integration and High-Level Transgene Expression in AAVS1 Transgenic Mice after In Vivo HSC Transduction with HDAd5/35++ Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion.Human gene therapy · 2019Article
- Retrograde monosynaptic tracing through an engineered human embryonic stem cell line reveals synaptic inputs from host neurons to grafted cells.Cell regeneration (London, England) · 2019Article
- Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies theF1000Research · 2019Article
- Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Sensitizing ovarian cancer cells to chemotherapy by interfering with pathways that are involved in the formation of cancer stem cells.Cancer biology & therapy · 2016Article
- CRISPR/Cas9-based genetic correction for recessive dystrophic epidermolysis bullosa.NPJ Regenerative medicine · 2016Article
- Efficient Recombinase-Mediated Cassette Exchange in hPSCs to Study the Hepatocyte Lineage Reveals AAVS1 Locus-Mediated Transgene Inhibition.Stem cell reports · 2015Article
- Excision of Expanded GAA Repeats Alleviates the Molecular Phenotype of Friedreich's Ataxia.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Achieving transgene integration into preselected genomic sites is currently one of the central tasks in stem cell gene therapy. A strategy to mediate such targeted integration involves site-specific endonucleases. Two genomic sites within the MBS85 and chemokine (C-C motif) receptor 5 (CCR5) genes (AAVS1 and CCR5 zinc-finger nuclease (CCR5-ZFN) sites, respectively) have recently been suggested as potential target regions for integration as their disruption has no functional consequence. We hypothesized that efficient transgene integration maybe affected by DNA accessibility of endonucleases and therefore studied the transcriptional and chromatin status of the AAVS1 and CCR5 sites in eight human induced pluripotent stem (iPS) cell lines and pooled CD34+ hematopoietic stem cells (HSCs). Matrix chromatin immunoprecipitation (ChIP) assays demonstrated that the CCR5 site and surrounding regions possessed a predominantly closed chromatin configuration consistent with its transcriptional inactivity in these cell types. In contrast, the AAVS1 site was located within a transcriptionally active region and exhibited an open chromatin configuration in both iPS cells and HSCs. To show that the AAVS1 site is readily amendable to genome modification, we expressed Rep78, an AAV2-derived protein with AAVS1-specific endonuclease activity, in iPS cells after adenoviral gene transfer. We showed that Rep78 efficiently associated with the AAVS1 site and triggered genome modifications within this site. On the other hand, binding to and modification of the CCR5-ZFN site by a ZFN was relatively inefficient. Our data suggest a critical influence of chromatin structure on efficacy of site-specific endonucleases used for genome editing.
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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.