T cell-specific siRNA delivery suppresses HIV-1 infection in humanized miceopen access
- Authors
- Kumar, Priti; Ban, Hong-Seok; Kim, Sang-Soo; Wu, Haoquan; Pearson, Todd; Greiner, Dale L.; Laouar, Amale; Yao, Jiahong; Haridas, Viraga; Habiro, Katsuyoshi; Yang, Yong-Guang; Jeong, Ji-Hoon; Lee, Kuen-Yong; Kim, Yong-Hee; Kim, Sung Wan; Peipp, Matthias; Fey, Georg H.; Manjunath, N.; Shultz, Leonard D.; Lee, Sang-Kyung; Shankar, Premlata
- Issue Date
- Aug-2008
- Publisher
- CELL PRESS
- Keywords
- CELLIMMUNO; HUMDISEASE
- Citation
- CELL, v.134, no.4, pp.577 - 586
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL
- Volume
- 134
- Number
- 4
- Start Page
- 577
- End Page
- 586
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/171930
- DOI
- 10.1016/j.cell.2008.06.034
- ISSN
- 0092-8674
- 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 (scFvCD79R) 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.
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