The CCR5 Gene Edited CD34⁺CD90⁺ Hematopoietic Stem Cell Population Serves as an Optimal Graft Source for HIV Gene Therapy.

ABSTRACT: Transplantation of allogenic hematopoietic stem and progenitor cells (HSPCs) with C-C chemokine receptor type 5 (CCR5) Δ32 genotype generates HIV-1 resistant immune cells. CCR5 gene edited autologous HSPCs can be a potential alternative to hematopoietic stem cell transplantation (HSCT) from HLA-matched CCR5 null donor. However, the clinical application of gene edited autologous HSPCs is critically limited by the quality of the graft, as HIV also infects the HSPCs. In this study, by using mobilized HSPCs from healthy donors, we show that the CD34⁺CD90⁺ hematopoietic stem cells (HSCs) express 7-fold lower CD4/CCR5 HIV receptors, higher levels of SAMHD1 anti-viral restriction factor, and possess lower susceptibility to HIV infection than the CD34⁺CD90^-

SUBMITTER: Karuppusamy KV 

PROVIDER: S-EPMC8963924 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature