Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates

Academic Article


  • RNAi is a powerful method for suppressing gene expression that has tremendous potential for therapeutic applications. However, because endogenous RNAi plays a role in normal cellular functions, delivery and expression of siRNAs must be balanced with safety. Here we report successful stable expression in primates of siRNAs directed to chemokine (c-c motif) receptor 5 (CCR5) introduced through CD34+ hematopoietic stem/progenitor cell transplant. After hematopoietic reconstitution, to date 14 months after transplant, we observe stably marked lymphocytes expressing siRNAs and consistent down-regulation of chemokine (c-c motif) receptor 5 expression. The marked cells are less susceptible to simian immunodeficiency virus infection ex vivo. These studies provide a successful demonstration that siRNAs can be used together with hematopoietic stem cell transplant to stably modulate gene expression in primates and potentially treat blood diseases such as HIV-1. © 2007 by The National Academy of Sciences of the USA.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Dong SA; Donahue RE; Kamata M; Poon B; Metzger M; Mao SH; Bonifacino A; Krouse AE; Darlix JL; Baltimore D
  • Start Page

  • 13110
  • End Page

  • 13115
  • Volume

  • 104
  • Issue

  • 32