| First Author | Kumar P | Year | 2008 |
| Journal | Cell | Volume | 134 |
| Issue | 4 | Pages | 577-86 |
| PubMed ID | 18691745 | Mgi Jnum | J:142409 |
| Mgi Id | MGI:3821489 | Doi | 10.1016/j.cell.2008.06.034 |
| Citation | Kumar P, et al. (2008) T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 134(4):577-86 |
| abstractText | 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. |
