Persistent hematopoietic polyclonality after lentivirus-mediated gene therapy for Fabry disease.

ABSTRACT: The safety and efficacy of lentivirus-mediated gene therapy was recently demonstrated in five male patients with Fabry disease-a rare X-linked lysosomal storage disorder caused by GLA gene mutations that result in multiple end-organ complications. To evaluate the risks of clonal dominance and leukemogenesis, which have been reported in multiple gene therapy trials, we conducted a comprehensive DNA insertion site analysis of peripheral blood samples from the five patients in our gene therapy trial. We found that patients had a polyclonal integration site spectrum and did not find evidence of a dominant clone in any patient. Although we identified vector integrations near proto-oncogenes, these had low percentages of contributions to the overall pool of integrations and did not persis

SUBMITTER: Saleh AH 

PROVIDER: S-EPMC9932294 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature