Unique Integration Profiles in a Canine Model of Long-Term Repopulating Cells Transduced with Gammaretrovirus, Lentivirus, or Foamy Virus
| Autor: | Michael A. Jacobs, Laura J. Peterson, Daniel G. Miller, Grant D. Trobridge, Hans-Peter Kiem, Rajinder Kaul, Kirsten A. Keyser, Brian C. Beard |
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| Rok vydání: | 2007 |
| Předmět: |
Virus Integration
Genetic enhancement Genetic Vectors In Vitro Techniques Transduction (genetics) Dogs Transduction Genetic Proto-Oncogenes Genetics medicine Animals Humans Spumavirus Molecular Biology DNA Primers Repetitive Sequences Nucleic Acid Gammaretrovirus Regulation of gene expression Base Sequence biology Lentivirus Hematopoietic stem cell Genetic Therapy biology.organism_classification Virology medicine.anatomical_structure Models Animal Molecular Medicine CpG Islands Safety |
| Zdroj: | Human Gene Therapy. 18:423-434 |
| ISSN: | 1557-7422 1043-0342 |
| DOI: | 10.1089/hum.2007.011 |
| Popis: | Recent advances have allowed for improved retrovirus-mediated gene transfer, and therapeutic benefits have been described in patients. These successes have shown the potential of hematopoietic stem cell (HSC) gene therapy, but treatment-related leukemia and benign expansion of gene-modified clones have shifted the attention toward safety. The delayed onset of adverse events in gene therapy clinical trials emphasizes the importance of long-term integration site studies in large animal models. We have addressed safety by characterizing the genomic location of 555 integration sites of the three most commonly used integrating retroviral vectors, that is, gammaretrovirus, lentivirus, and foamy virus, in long-term repopulating cells from dogs. Gammaretroviral integrants showed the most significant frequency of occurrence very close ( |
| Databáze: | OpenAIRE |
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