We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3+ T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34+ progenitor cells derived from 1 further patient and 1 healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34+ progenitors during transduction. In contrast to those in CD34+ cells, RISs recovered from engrafted CD3+ T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation.
Kerstin Schwarzwaelder, Steven J. Howe, Manfred Schmidt, Martijn H. Brugman, Annette Deichmann, Hanno Glimm, Sonja Schmidt, Claudia Prinz, Manuela Wissler, Douglas J.S. King, Fang Zhang, Kathryn L. Parsley, Kimberly C. Gilmour, Joanna Sinclair, Jinhua Bayford, Rachel Peraj, Karin Pike-Overzet, Frank J.T. Staal, Dick de Ridder, Christine Kinnon, Ulrich Abel, Gerard Wagemaker, H. Bobby Gaspar, Adrian J. Thrasher, Christof von Kalle
Usage data is cumulative from August 2023 through August 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 321 | 62 |
113 | 23 | |
Figure | 121 | 7 |
Table | 140 | 0 |
Supplemental data | 26 | 0 |
Citation downloads | 37 | 0 |
Totals | 758 | 92 |
Total Views | 850 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.