期刊
MOLECULAR THERAPY
卷 18, 期 10, 页码 1803-1813出版社
CELL PRESS
DOI: 10.1038/mt.2010.141
关键词
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资金
- Children's Cancer Research Fund in Minneapolis, Alliance for Cancer Gene Therapy
- Gabrielle's Angel (formerly G&P) Foundation for Cancer Research
- Sidney Kimmel Foundation for Cancer Research
- University of Minnesota
- University Minnesota Medical School Dean's Commitment
- Leukemia Research Fund
- American Society of Hematology
- Undergraduate Research Opportunity Program Award
- Multicultural Summer Research Opportunities Award
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
In this study, we compared the genomic integration efficiencies and transposition site preferences of Sleeping Beauty (SB or SB11), Tol2, and piggyBac (PB) transposon systems in primary T cells derived from peripheral blood lymphocytes (PBL) and umbilical cord blood (UCB). We found that PB demonstrated the highest efficiency of stable gene transfer in PBL-derived T cells, whereas SB11 and Tol2 mediated intermediate and lowest efficiencies, respectively. Southern hybridization analysis demonstrated that PB generated the highest number of integrants when compared to SB and Tol2 in both PBL and UCB T cells. Tol2 and PB appeared more likely to promote clonal expansion than SB, which may be in part due to the dysregulated expression of cancer-related genes near the insertion sites. Genome-wide integration analysis demonstrated that SB, Tol2, and PB integrations occurred in all the chromosomes without preference. Additionally, Tol2 and PB integration sites were mainly localized near transcriptional start sites (TSSs), CpG islands and DNasel hypersensitive sites, whereas SB integrations were randomly distributed. These results suggest that SB may be a preferential choice of the delivery vector in T cells due to its random integration site preference and relatively high efficiency, and support continuing development of SB-mediated T-cell phase I trials.
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