| Autor: |
Perez, Elena E, Wang, Jianbin, Miller, Jeffrey C, Jouvenot, Yann, Kim, Kenneth A, Liu, Olga, Wang, Nathaniel, Lee, Gary, Bartsevich, Victor V, Lee, Ya-Li, Guschin, Dmitry Y, Rupniewski, Igor, Waite, Adam J, Carpenito, Carmine, Carroll, Richard G, S Orange, Jordan, Urnov, Fyodor D, Rebar, Edward J, Ando, Dale, Gregory, Philip D |
| Předmět: |
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| Zdroj: |
Nature Biotechnology; Jul2008, Vol. 26 Issue 7, p808-816, 9p, 1 Black and White Photograph, 3 Graphs |
| Abstrakt: |
Homozygosity for the naturally occurring Δ32 deletion in the HIV co-receptor CCR5 confers resistance to HIV-1 infection. We generated an HIV-resistant genotype de novo using engineered zinc-finger nucleases (ZFNs) to disrupt endogenous CCR5. Transient expression of CCR5 ZFNs permanently and specifically disrupted ∼50% of CCR5 alleles in a pool of primary human CD4+ T cells. Genetic disruption of CCR5 provided robust, stable and heritable protection against HIV-1 infection in vitro and in vivo in a NOG model of HIV infection. HIV-1-infected mice engrafted with ZFN-modified CD4+ T cells had lower viral loads and higher CD4+ T-cell counts than mice engrafted with wild-type CD4+ T cells, consistent with the potential to reconstitute immune function in individuals with HIV/AIDS by maintenance of an HIV-resistant CD4+ T-cell population. Thus adoptive transfer of ex vivo expanded CCR5 ZFN–modified autologous CD4+ T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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