Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases.
Nat Biotechnol
; 26(7): 808-16, 2008 Jul.
Article
em En
| MEDLINE
| ID: mdl-18587387
ABSTRACT
Homozygosity for the naturally occurring Delta32 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 approximately 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Infecções por HIV
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Dedos de Zinco
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Transferência Adotiva
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Desoxirribonucleases
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article