T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice.
Document Type
Article
Publication Date
2008
Keywords
Antigens-CD7, Disease-Models-Animal, Gene-Expression, HIV-Infections, HIV-1, Humans, Immunoglobulin-Fragments, Immunoglobulin-Variable-Region, Leukocytes-Mononuclear, Mice-Inbred-NOD, Mice-SCID, RNA-Interference, RNA-Small-Interfering, RNA-Viral, T-Lymphocytes
First Page
577
Last Page
586
JAX Source
Cell 2008 Aug; 134(4):577-86.
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.
Recommended Citation
Kumar P,
Ban HS,
Kim SS,
Wu H,
Pearson T,
Greiner DL,
Lee KY,
Peipp M,
Fey GH,
Manjunath N,
Shultz LD,
Lee SK,
et a.
T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 2008 Aug; 134(4):577-86.