ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Biosafety assessment of site-directed transgene integration in human umbilical cord-lining cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Revisiting the human umbilical cord epithelium. An atypical epithelial sheath with distinctive features.Cell and tissue research · 2024Article
- Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome.Nature biotechnology · 2023Article
- Human Umbilical Cord Lining-Derived Epithelial Cells: A Potential Source of Non-Native Epithelial Cells That Accelerate Healing in a Porcine Cutaneous Wound Model.International journal of molecular sciences · 2022Article
- Site-specific integration as an efficient method for production of recombinant human hyaluronidase PH20 in semi-adherent cells.Applied microbiology and biotechnology · 2022Article
- Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Corneal Epithelial Repair In Vitro.Cells · 2021Article
- Tissue-Cultured Human Cord Lining Epithelial Cells in Treatment of Persistent Corneal Epithelial Defect.Open access Macedonian journal of medical sciences · 2019Article
- Global mapping of binding sites for phic31 integrase in transgenic maden-darby bovine kidney cells using ChIP-seq.Hereditas · 2019Article
- Short review on human umbilical cord lining epithelial cells and their potential clinical applications.Stem cell research & therapy · 2017Review
- Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Long-term and efficient expression of human β-globin gene in a hematopoietic cell line using a new site-specific integrating non-viral system.Gene therapy · 2015Article
- Neuroprotective therapies in glaucoma: II. Genetic nanotechnology tools.Frontiers in neuroscience · 2015Review
- PhiC31 integrase induces efficient site-specific recombination in the Capra hircus genome.DNA and cell biology · 2014Article
- Intragenic integration in DLC1 sustains factor VIII expression in primary human cells without insertional oncogenicity.Gene therapy · 2014Article
- Cord lining-mesenchymal stem cells graft supplemented with an omental flap induces myocardial revascularization and ameliorates cardiac dysfunction in a rat model of chronic ischemic heart failure.Tissue engineering. Part A · 2013Article
- Advanced therapies for the treatment of hemophilia: future perspectives.Orphanet journal of rare diseases · 2012Review
- Long-term expression of human coagulation factor VIII in a tolerant mouse model using the φC31 integrase system.Human gene therapy · 2012Article
- Umbilical cord lining stem cells as a novel and promising source for ocular surface regeneration.Stem cell reviews and reports · 2011Article
- Reliable transgene-independent method for determining Sleeping Beauty transposon copy numbers.Mobile DNA · 2011Article
- Impact of hydrodynamic injection and phiC31 integrase on tumor latency in a mouse model of MYC-induced hepatocellular carcinoma.PloS one · 2010Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biosafety and efficacy considerations that impede clinical application of gene therapy could be addressed by nonviral ex vivo cell therapy, utilizing transgenic cells that have been comprehensively pre-evaluated for genotoxic potential and transgene expression. We evaluated the genotoxic potential of phiC31 bacteriophage integrase-mediated transgene integration in cord-lining epithelial cells (CLECs) readily cultured from the outer membrane of human umbilical cords, by sequencing and mapping integration sites, spectral karyotyping, high-resolution genome copy number, transcriptome, and transgene copy number analyses and in vivo tumorigenicity. Of 44 independent integration events, <5% were exonic and 85% of modified cells had integrated <or=2 transgene(s). Expression of 95.6% of genes was unaltered in modified cells. Only three small regions showed genome copy number changes that did not correlate with altered gene expression or integration sites. Spectral karyotyping revealed rare nonrecurrent occurrence of three different translocations. Integrase-modified cells were not tumorigenic in immunocompromised mice for at least 4 months. Stable integration of a human factor VIII (FVIII) construct conferred durable FVIII secretion in vitro. Xenoimplantation of FVIII-secreting CLECs in immunocompetent hemophilic mice achieved significant phenotypic correction. Pre-evaluated clonal populations of phiC31 integrase-modified CLECs could be useful as bioimplants for monogenic diseases such as hemophilia.
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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.