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
Rok vydání: 2009
Předmět:
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