Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells.

ABSTRACT: Clinical application of lentiviral vector (LV)-based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV-mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on the HSPC transcriptional landscape. LV escaped innate immune sensing that instead led to robust IFN responses upon transduction with a gamma-retroviral vector. However, reverse-transcribed LV DNA did trigger p53 signaling, activated also by non-integrating Adeno-associated vector, ultimately leading to lower cell recovery ex vivo and engraftment in vivo These effects were more pronounced in the short-term repopulating cells while long-term HSC frequencies remained

SUBMITTER: Piras F 

PROVIDER: S-EPMC5582409 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature