Journal article

An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation

Byoung Y Ryu, Marguerite V Evans-Galea, John T Gray, David M Bodine, Derek A Persons, Arthur W Nienhuis

BLOOD | AMER SOC HEMATOLOGY | Published : 2008


Pathogenic activation of the LMO2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for X-linked severe combined immunodeficiency (X-SCID) has prompted safety concerns. We used an adeno-associated virus vector to achieve targeted insertion of a gamma-retroviral long terminal repeat (LTR) driving a GFP expression cassette with flanking loxP sites in a human T-cell line at the precise location of vector integration in one of the patients with X-SCID. The LTR-GFP cassette was inserted into the first intron of the LMO2 gene, resulting in strong activation of LMO2. Cre-mediated cassette exchange was used to replace the original LTR-GFP cassette with one flanked by insulator..

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