T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice Export

@article{citeulike:3106237, abstract = {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/SCIDIL2r[gamma]-/- 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.}, author = {Kumar, Priti and Ban, Hong-Seok and Kim, Sang-Soo and Wu, Haoquan and Pearson, Todd and Greiner, Dale L. and Laouar, Amale and Yao, Jiahong and Haridas, Viraga and Habiro, Katsuyoshi and Yang, Yong-Guang and Jeong, Ji-Hoon and Lee, Kuen-Yong and Kim, Yong-Hee and Kim, Sung W. and Peipp, Matthias and Fey, Georg H. and Manjunath, N. and Shultz, Leonard D. and Lee, Sang-Kyung and Shankar, Premlata}, citeulike-article-id = {3106237}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2008.06.034}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18691745}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18691745}, citeulike-linkout-3 = {http://www.sciencedirect.com/science/article/B6WSN-4T5BRBH-1/2/3922a3605fa01ca36429dadc349e468f}, doi = {10.1016/j.cell.2008.06.034}, journal = {Cell}, keywords = {cd4, cd8, hiv, journalclub, sirna, viral-delivery}, posted-at = {2008-08-25 18:42:03}, priority = {2}, title = {T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice}, url = {http://dx.doi.org/10.1016/j.cell.2008.06.034}, volume = {In Press, Corrected Proof} }

TY - JOUR ID - citeulike:3106237 L3 - citeulike-article-id:3106237 N2 - 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/SCIDIL2r[gamma]-/- 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. JF - Cell TI - T Cell-Specific siRNA Delivery Suppresses HIV-1 Infection in Humanized Mice VL - In Press, Corrected Proof KW - cd4 KW - cd8 KW - hiv KW - journalclub KW - sirna KW - viral-delivery AU - Kumar, Priti AU - Ban, Hong-Seok AU - Kim, Sang-Soo AU - Wu, Haoquan AU - Pearson, Todd AU - Greiner, Dale AU - Laouar, Amale AU - Yao, Jiahong AU - Haridas, Viraga AU - Habiro, Katsuyoshi AU - Yang, Yong-Guang AU - Jeong, Ji-Hoon AU - Lee, Kuen-Yong AU - Kim, Yong-Hee AU - Kim, Sung AU - Peipp, Matthias AU - Fey, Georg AU - Manjunath, N AU - Shultz, Leonard AU - Lee, Sang-Kyung AU - Shankar, Premlata UR - http://dx.doi.org/10.1016/j.cell.2008.06.034 ER -