@article{3152040,
    title = "The New Self-Inactivating Lentiviral Vector for Thalassemia Gene Therapy
Combining Two HPFH Activating Elements Corrects Human Thalassemic
Hematopoietic Stem Cells",
    author = "Papanikolaou, Eleni and Georgomanoli, Maria and Stamateris, Evangelos and and Panetsos, Fottes and Karagiorga, Markisia and Tsaftaridis, and Panagiotis and Graphakos, Stelios and Anagnou, Nicholas P.",
    journal = "Human Gene Therapy",
    year = "2012",
    volume = "23",
    number = "1",
    pages = "15-31",
    publisher = "MARY ANN LIEBERT INC PUBL",
    issn = "1043-0342, 1557-7422",
    doi = "10.1089/hum.2011.048",
    abstract = "To address how low titer, variable expression, and gene silencing affect
gene therapy vectors for hemoglobinopathies, in a previous study we
successfully used the HPFH (hereditary persistence of fetal
hemoglobin)-2 enhancer in a series of oncoretroviral vectors. On the
basis of these data, we generated a novel insulated self-inactivating
(SIN) lentiviral vector, termed GGHI, carrying the (A)gamma-globin gene
with the -117 HPFH point mutation and the HPFH-2 enhancer and exhibiting
a pancellular pattern of (A)gamma-globin gene expression in MEL-585
clones. To assess the eventual clinical feasibility of this vector, GGHI
was tested on CD34(+) hematopoietic stem cells from nonmobilized
peripheral blood or bone marrow from 20 patients with beta-thalassemia.
Our results show that GGHI increased the production of gamma-globin by
32.9% as measured by high-performance liquid chromatography ( p=0.001),
with a mean vector copy number per cell of 1.1 and a mean transduction
efficiency of 40.3%. Transduced populations also exhibited a lower rate
of apoptosis and resulted in improvement of erythropoiesis with a higher
percentage of orthochromatic erythroblasts. This is the first report of
a locus control region (LCR)-free SIN insulated lentiviral vector that
can be used to efficiently produce the anticipated therapeutic levels of
gamma-globin protein in the erythroid progeny of primary human
thalassemic hematopoietic stem cells in vitro."
}