Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells.

ABSTRACT: Recent reports linking insertional activation of LMO2 following gene therapy for X-linked severe combined immunodeficiency (X-SCID) have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34+ cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals. Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells. We hypothesize that this over-representation likely results from an impact on the self-renewal and engraftment potential of CD34+ progenitor cells via insert

SUBMITTER: Calmels B 

PROVIDER: S-EPMC1895268 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature