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- Title
Establishment of HIV-1 resistance in CD4<sup>+</sup> T cells by genome editing using zinc-finger nucleases.
- Authors
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
- Abstract
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.
- Subjects
HIV; CD4 antigen; IMMUNOGENETICS; NUCLEASES; ZINC-finger proteins; HIV infections; GENETICS
- Publication
Nature Biotechnology, 2008, Vol 26, Issue 7, p808
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt1410