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

• DOI: 10.1073/pnas.0705474104
• Publication Date: 2007-08-02T01:00:31Z
• Authors: Dong Sung An; Robert E. Donahue; Masakazu Kamata; Betty Poon; Mark Metzger; Si-Hua Mao; Aylin Bonifacino; Allen E. Krouse; Jean-Luc Darlix; David Baltimore; F. Xiao-Feng Qin; Irvin S. Y. Chen
• Keywords: Hematopoietic stem cell; Chemokine receptor CCR5

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