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Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
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Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
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Journal Article
Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases
2008
Overview
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ CD4-Positive T-Lymphocytes - enzymology
/ CD4-Positive T-Lymphocytes - transplantation
/ Chromosome Mapping - methods
/ Deoxyribonucleases - genetics
/ Fundamental and applied biological sciences. Psychology
/ Genetic Engineering - methods
/ Genomics
/ Health. Pharmaceutical industry
/ HIV
/ HIV Infections - prevention & control
/ Human immunodeficiency virus
/ Humans
/ Industrial applications and implications. Economical aspects
/ Mice
/ Zinc
