Title
T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Medicine, Division of Diabetes; Immune Disease Institute and Department of Pediatrics
Publication Date
2008-08-12
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
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/SCIDIL2rgamma-/- 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.
DOI of Published Version
10.1016/j.cell.2008.06.034
Source
Cell. 2008 Aug 22;134(4):577-86. Epub 2008 Aug 7. Link to article on publisher's site
Journal/Book/Conference Title
Cell
Related Resources
PubMed ID
18691745
Repository Citation
Kumar PD, Ban H, Kim S, Wu H, Pearson T, Greiner DL, Laouar A, Yao J, Haridas V, Habiro K, Yang Y, Jeong J, Lee K, Kim Y, Kim S, Peipp M, Fey GH, Manjunath N, Shultz LD, Lee S, Shankar P. (2008). T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. GSBS Student Publications. https://doi.org/10.1016/j.cell.2008.06.034. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1576