| Title |
Deletion of the LTR Enhancer/Promoter Has No Impact on the Integration Profile of MLV Vectors in Human Hematopoietic Progenitors
|
|---|---|
| Published in |
PLOS ONE, January 2013
|
| DOI | 10.1371/journal.pone.0055721 |
| Pubmed ID | |
| Authors |
Arianna Moiani, Annarita Miccio, Ermanno Rizzi, Marco Severgnini, Danilo Pellin, Julia Debora Suerth, Christopher Baum, Gianluca De Bellis, Fulvio Mavilio |
| Abstract |
Moloney murine leukemia virus (MLV)-derived gamma-retroviral vectors integrate preferentially near transcriptional regulatory regions in the human genome, and are associated with a significant risk of insertional gene deregulation. Self-inactivating (SIN) vectors carry a deletion of the U3 enhancer and promoter in the long terminal repeat (LTR), and show reduced genotoxicity in pre-clinical assays. We report a high-definition analysis of the integration preferences of a SIN MLV vector compared to a wild-type-LTR MLV vector in the genome of CD34(+) human hematopoietic stem/progenitor cells (HSPCs). We sequenced 13,011 unique SIN-MLV integration sites and compared them to 32,574 previously generated MLV sites in human HSPCs. The SIN-MLV vector recapitulates the integration pattern observed for MLV, with the characteristic clustering of integrations around enhancer and promoter regions associated to H3K4me3 and H3K4me1 histone modifications, specialized chromatin configurations (presence of the H2A.Z histone variant) and binding of RNA Pol II. SIN-MLV and MLV integration clusters and hot spots overlap in most cases and are generated at a comparable frequency, indicating that the reduced genotoxicity of SIN-MLV vectors in hematopoietic cells is not due to a modified integration profile. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 3% |
| Unknown | 37 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 12 | 32% |
| Researcher | 12 | 32% |
| Student > Master | 4 | 11% |
| Other | 3 | 8% |
| Student > Bachelor | 2 | 5% |
| Other | 3 | 8% |
| Unknown | 2 | 5% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 15 | 39% |
| Biochemistry, Genetics and Molecular Biology | 8 | 21% |
| Immunology and Microbiology | 4 | 11% |
| Medicine and Dentistry | 4 | 11% |
| Nursing and Health Professions | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 5 | 13% |