Gene therapy for severe combined immunodeficiency: are we there yet?
J. Clin. Invest. Marina Cavazzana-Calvo, et al. 117:1456 doi:10.1172/JCI30953 [
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Figure 2Schematic representation of retroviral vectors and their modifications to improve safety. (
A) The transcription of the therapeutic gene is driven by the enhancer-promoter activity of the U
3 region of the retroviral LTR. (
B) The transcription of the therapeutic gene is driven by the addition of an internal promoter. The U
3 region of the retroviral LTR has been almost completely deleted. (
C) The provirus contains the cHS4 element (i.e., insulator) in order to protect the transcriptional cassette against position effects. (
D) This provirus contains 2 cassettes: (a) the therapeutic gene driven by a first internal promoter and (b) a suicide gene (e.g., thymidine kinase,
TK) that could allow the elimination of gene-corrected cells if an adverse event such as a monoclonal proliferation occurs. EF-1a, elongation factor–1a; IRES, internal ribosome entry site; PGK, phosphoglycerate kinase; R, repeats; SA, site acceptor; SD, site donor.
