Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells

被引：60

作者：

Chang, Chan-Jung ^{[1
]}

Bouhassira, Eric E. ^{[1
]}

机构：

[1] Albert Einstein Coll Med, Dept Cell Biol, Div Hematol, Dept Med, Bronx, NY 10461 USA

来源：

BLOOD | 2012年 / 120卷 / 19期

基金：

美国国家卫生研究院;

关键词：

EMBRYONIC STEM-CELLS; COPY NUMBER; GENETIC CORRECTION; HUMAN ESCS; MUTATION; PLURIPOTENCY; ACTIVATION; THERAPY; PATIENT; MODEL;

D O I：

10.1182/blood-2012-03-420703

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Induced pluripotent stem (iPS) cell technology holds vast promises for a cure to the hemoglobinopathies. Constructs and methods to safely insert therapeutic genes to correct the genetic defect need to be developed. Site-specific insertion is a very attractive method for gene therapy because the risks of insertional mutagenesis are eliminated provided that a "safe harbor" is identified, and because a single set of validated constructs can be used to correct a large variety of mutations simplifying eventual clinical use. We report here the correction of alpha-thalassemia major hydrops fetalis in transgene-free iPS cells using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on human chromosome 19. Homozygous insertion of the best of the 4 constructs tested led to complete correction of globin chain imbalance in erythroid cells differentiated from the corrected iPS cells. (Blood. 2012;120(19):3906-3914)

引用

页码：3906 / 3914

页数：9

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