Genome-wide mapping of PiggyBac transposon integrations in primary human T cells
Autor: | Matthew H. Wilson, Yozo Nakazawa, Claudia Kettlun, Aparna Kaja, Cliona M. Rooney, Daniel L. Galvan, Laurence J.N. Cooper |
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Rok vydání: | 2009 |
Předmět: |
Transposable element
Cancer Research animal structures Genetic enhancement T-Lymphocytes Immunology Genetic Vectors Biology Gene delivery Genome Immunotherapy Adoptive Article Immunology and Allergy Humans Gene Pharmacology Genetics Mutagenicity Tests HEK 293 cells fungi Lentivirus PiggyBac Transposon System DNA Transposable Elements Human genome CpG Islands Gammaretrovirus Transcription Initiation Site Genome-Wide Association Study HeLa Cells |
Zdroj: | Journal of immunotherapy (Hagerstown, Md. : 1997). 32(8) |
ISSN: | 1537-4513 |
Popis: | The piggyBac transposon system represents a promising nonviral tool for gene delivery and discovery, and may also be of value for clinical gene therapy. PiggyBac is a highly efficient integrating vector that stably transfects (approximately 40%) of primary human T cells for potential adoptive immunotherapy applications. To evaluate the potential genotoxicity of piggyBac, we compared 228 integration sites in primary human T cells to integrations in 2 other human-derived cell lines (HEK293 and HeLa) and randomly simulated integrations into the human genome. Our results revealed distinct differences between cell types. PiggyBac had a nonrandom integration profile and a preference for transcriptional units (approximately 50% into RefSeq genes in all cell types), CpG islands (18% in T cells and 8% in other human cells), and transcriptional start sites ( |
Databáze: | OpenAIRE |
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