Author/Authors :
Priti Kumar، نويسنده , , Hong-Seok Ban، نويسنده , , Sang-Soo Kim، نويسنده , , Haoquan Wu، نويسنده , , Todd Pearson، نويسنده , , Dale L. Greiner، نويسنده , , Amale Laouar، نويسنده , , Jiahong Yao، نويسنده , , Viraga Haridas، نويسنده , , Katsuyoshi Habiro، نويسنده , , Yong-Guang Yang، نويسنده , , Ji Hoon Jeong، نويسنده , , Kuen Yong Lee، نويسنده , , Yong-Hee Kim، نويسنده , , Sung Wan Kim، نويسنده , , Matthias Peipp، نويسنده , , Georg H. Fey، نويسنده , , N. Manjunath، نويسنده , , Leonard D. Shultz، نويسنده , , Sang Kyung Lee، نويسنده , , et al.، نويسنده ,
Abstract :
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.
