التفاصيل البيبلوغرافية
| العنوان: |
Lentiviral vector integration sites in human NOD/SCID repopulating cells |
| المؤلفون: |
Laufs, Stephanie, Guenechea, Guillermo, Gonzalez‐Murillo, Africa, Zsuzsanna Nagy, K., Luz Lozano, M., del Val, Coral, Jonnakuty, Sunitha, Hotz‐Wagenblatt, Agnes, Jens Zeller, W., Bueren, Juan A., Fruehauf, Stefan |
| المصدر: |
The Journal of Gene Medicine ; volume 8, issue 10, page 1197-1207 ; ISSN 1099-498X 1521-2254 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2006 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Background Recent observations of insertional mutagenesis in preclinical and clinical settings emphasize the relevance of investigating comprehensively the spectrum of integration sites targeted by specific vectors. Methods We followed the engraftment of lentivirally transduced human cord blood (CB) progenitor cells after transplantation into NOD/SCID mice using a self‐inactivating HIV‐1‐derived vector expressing the enhanced green fluorescent protein (EGFP). Results The mean of transduction of CD34 + CB cells was 41%, as deduced from the percentage of EGFP + cells before transplantation. At 3 weeks post‐transplantation, the average of EGFP + cells in the human cell population was 65 ± 8%, and increased to 75 ± 10% at 12 weeks post‐transplantation. In order to determine the proviral integration sites in human NOD/SCID repopulating cells (SRCs) we used the ligation‐mediated polymerase chain reaction (LM‐PCR) technique. Sixty‐eight percent of the integrations were found to be located in RefSeq genes, most of them in intron regions. Twenty percent of these integrations occurred within a distance of 10 kb from the transcription start site; a percentage that is significantly lower compared to that observed in cells transduced by gammaretroviral vectors. Sixty‐two percent of integrations occurred in genes with a biological function in cell metabolism, and four integrations were located in genes with a role in tumorigenesis. Conclusions These investigations indicate that integration of lentiviral vectors in human repopulating cells capable of engrafting NOD/SCID mice preferentially occur in coding regions of the human genome. Nevertheless, the clustering of integrations at the transcriptional start is not as high as that observed for gammaretroviral vectors. Copyright © 2006 John Wiley & Sons, Ltd. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/jgm.958 |
| الإتاحة: |
https://doi.org/10.1002/jgm.958Test |
| حقوق: |
http://onlinelibrary.wiley.com/termsAndConditions#vorTest |
| رقم الانضمام: |
edsbas.1A34FC4B |
| قاعدة البيانات: |
BASE |
