T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice

被引：500

作者：

Kumar, Priti ^{[3
,4
]}

Ban, Hong-Seok ^{[1
,2
]}

Kim, Sang-Soo ^{[3
,4
]}

Wu, Haoquan ^{[3
,4
]}

Pearson, Todd ^{[5
]}

Greiner, Dale L. ^{[5
]}

Laouar, Amale ^{[3
,4
]}

Yao, Jiahong ^{[3
,4
]}

Haridas, Viraga ^{[3
,4
]}

Habiro, Katsuyoshi ^{[6
]}

Yang, Yong-Guang ^{[6
]}

Jeong, Ji-Hoon ^{[7
]}

Lee, Kuen-Yong ^{[1
,2
]}

Kim, Yong-Hee ^{[1
,2
]}

Kim, Sung Wan ^{[7
]}

Peipp, Matthias ^{[8
]}

Fey, Georg H. ^{[9
]}

Manjunath, N. ^{[3
,4
]}

Shultz, Leonard D. ^{[10
]}

Lee, Sang-Kyung ^{[1
,2
]}

Shankar, Premlata ^{[3
,4
]}

机构：

[1] Hanyang Univ, Dept Bioengn, Seoul 133791, South Korea

[2] Hanyang Univ, Hanyang Fus Mat Program, Seoul 133791, South Korea

[3] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[5] Univ Massachusetts, Sch Med, Dept Med, Div Diabet, Worcester, MA 01605 USA

[6] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA

[7] Univ Utah, Ctr Controlled Chem Delivery, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA

[8] Univ Kiel, Div Stem Cell Transplantat & Immunotherapy, D-24105 Kiel, Germany

[9] Univ Erlangen Nurnberg, D-91058 Erlangen, Germany

[10] Jackson Lab, Bar Harbor, ME 04609 USA

来源：

CELL | 2008年 / 134卷 / 04期

关键词：

D O I：

10.1016/j.cell.2008.06.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (scFvCD79R) for T cell-specific siRNA delivery in NOD/SCIDIL2r gamma(-/-) 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.

引用

页码：577 / 586

页数：10

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