Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo.

ABSTRACT: 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

SUBMITTER: Schwarzwaelder K 

PROVIDER: S-EPMC1934556 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature