T Cell-specific SiRNA Delivery Suppresses HIV-1 Infection in Humanized Mice

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2008 Aug 12

PMID 18691745

Citations 254

Authors

Priti Kumar

Hong-Seok Ban

Sang-Soo Kim

Haoquan Wu

Todd Pearson

Dale L Greiner

Amale Laouar

Jiahong Yao

Viraga Haridas

Katsuyoshi Habiro

Yong-Guang Yang

Ji-Hoon Jeong

Kuen-Yong Lee

Yong-Hee Kim

Sung Wan Kim

Matthias Peipp

Georg H Fey

N Manjunath

Leonard D Shultz

Sang-Kyung Lee

Premlata Shankar

Affiliations

Soon will be listed here.

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.

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