Authors:
Priti Kumar, Hong-Seok Ban, Sang-Soo Kim, Haoquan Wu, Todd Pearson, Dale L. Greiner, Amale Laouar, Jiahong Yao, Viraga Haridas, Katsuyoshi Habiro, Yong-Guang Yang, Ji-Hoon Jeong, Kuen-Yong Lee, Yong-Hee Kim, Sung Wan Kim, Matthias Peipp, Georg H. Fey, N. Manjunath, Leonard D. Shultz, Sang-Kyung Lee, and Premlata Shankar
Summary:
Evaluation of the therapeutic potential of RNAi for HIV infection has been hampered by the challenges of siRNA delivery and lack of suitable animal models. Using a delivery method for T cells, we show that siRNA treatment can dramatically suppress HIV infection. A CD7-specific single-chain antibody was conjugated to oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2rγ−/− mice reconstituted with human lymphocytes (Hu-PBL) or CD34+ hematopoietic stem cells (Hu-HSC). In HIV-infected Hu-PBL mice, treatment with anti-CCR5 (viral coreceptor) and antiviral siRNAs complexed to scFvCD7-9R controlled viral replication and prevented the disease-associated CD4 T cell loss. This treatment also suppressed endogenous virus and restored CD4 T cell counts in mice reconstituted with HIV+ peripheral blood mononuclear cells. Moreover, scFvCD7-9R could deliver antiviral siRNAs to naive T cells in Hu-HSC mice and effectively suppress viremia in infected mice. Thus, siRNA therapy for HIV infection appears to be feasible in a preclinical animal model.
Source:
Cell; Vol. 134, 577-586 (08/22/08)