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

Link to Article in PubMed

PubMed ID

18691745

Link to Full Text

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