Unique Integration Profiles in a Canine Model of Long-Term Repopulating Cells Transduced with Gammaretrovirus, Lentivirus, or Foamy Virus

摘要: Recent advances have allowed for improved retrovirus-mediated gene transfer, and therapeutic benefits been described in patients. These successes shown the potential of hematopoietic stem cell (HSC) therapy, but treatment-related leukemia benign expansion gene-modified clones shifted attention toward safety. The delayed onset adverse events therapy clinical trials emphasizes importance long-term integration site studies large animal models. We addressed safety by characterizing genomic location 555 sites three most commonly used integrating retroviral vectors, that is, gammaretrovirus, lentivirus, foamy virus, repopulating cells from dogs. Gammaretroviral integrants showed significant frequency occurrence very close (<2.5 kb) to transcription start sites, a substantial portion all were within 50 kb. Importantly, gammaretroviral found more freque...