<p>Previously, we confirmed that BaEV-LVs outperformed VSV-G-LVs for gene delivery or correction of human T cells, B cells, NK cells and HSPCs correlating with high expression of its receptors, ASCT-1 and ASCT-2 on these cells. Since HERV-W gp uses the same entry receptors, we compared transduction efficiencies for BaEV-LVs and HERV-W-LVs in hematopoietic cells. HERV-W LV transduction was efficient but inferior to BaEV-LV in TCR-stimulated T cells (40% versus 80%) and this low efficiency was even more pronounced in IL-7/IL-15 pre-stimulated T cells. BaEV-LVs were significantly superior over HERV-W-LVs for the transduction of B cells and NK cells. High HERV-W-LV mediated transduction levels were achieved for pre-stimulated hCD34+ cells, which remained though lower than for the BaEV-LVs. Additionally, BaEV-LVs reached over 80% of transduction in severe combined immunodeficiency (SCID) repopulating cells (SRC) in 6/6 engrafted NBSGW mice. HERV-W-LVs reached this transduction level in 1/5 mice, while 3/5 engrafted NBSGW mice reached significantly lower transduction levels (20–50%). For both vectors the transduction levels were equivalent in the lymphoid and myeloid lineages in all hematopoietic tissues, suggesting transduction of immature HSPCs. Summarizing, BaEV-LVs outperformed HERV-W-LVs for transduction of important gene therapy target cells such as NK, B, T cells and CD34+ HSPCs.</p>

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Baboon endogenous retrovirus (ERV) envelope pseudotyped lentiviral vectors outperform human ERV lentivectors for transduction of T, B, NK and HSPCs

  • Séverine Périan,
  • Eva Castellano,
  • Caroline Costa,
  • Chiara Martinello,
  • Anne Galy,
  • Gisèle Froment,
  • Rimas Orentas,
  • Antonio Valeri,
  • Els Verhoeyen

摘要

Previously, we confirmed that BaEV-LVs outperformed VSV-G-LVs for gene delivery or correction of human T cells, B cells, NK cells and HSPCs correlating with high expression of its receptors, ASCT-1 and ASCT-2 on these cells. Since HERV-W gp uses the same entry receptors, we compared transduction efficiencies for BaEV-LVs and HERV-W-LVs in hematopoietic cells. HERV-W LV transduction was efficient but inferior to BaEV-LV in TCR-stimulated T cells (40% versus 80%) and this low efficiency was even more pronounced in IL-7/IL-15 pre-stimulated T cells. BaEV-LVs were significantly superior over HERV-W-LVs for the transduction of B cells and NK cells. High HERV-W-LV mediated transduction levels were achieved for pre-stimulated hCD34+ cells, which remained though lower than for the BaEV-LVs. Additionally, BaEV-LVs reached over 80% of transduction in severe combined immunodeficiency (SCID) repopulating cells (SRC) in 6/6 engrafted NBSGW mice. HERV-W-LVs reached this transduction level in 1/5 mice, while 3/5 engrafted NBSGW mice reached significantly lower transduction levels (20–50%). For both vectors the transduction levels were equivalent in the lymphoid and myeloid lineages in all hematopoietic tissues, suggesting transduction of immature HSPCs. Summarizing, BaEV-LVs outperformed HERV-W-LVs for transduction of important gene therapy target cells such as NK, B, T cells and CD34+ HSPCs.