GSBS Student Publications

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

Date

8-12-2008

Document Type

Article

Medical Subject Headings

Animals; Antigens, CD7; Disease Models, Animal; Gene Expression; HIV Infections; HIV-1; Humans; Immunoglobulin Fragments; Immunoglobulin Variable Region; Leukocytes, Mononuclear; Mice; Mice, Inbred NOD; Mice, SCID; *RNA Interference; RNA, Small Interfering; RNA, Viral; T-Lymphocytes

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.

Rights and Permissions

Citation: Cell. 2008 Aug 22;134(4):577-86. Epub 2008 Aug 7. Link to article on publisher's site

DOI of Published Version

10.1016/j.cell.2008.06.034

Related Resources

Link to Article in PubMed

Journal Title

Cell

PubMed ID

18691745