(A) The transcription of the therapeutic gene is driven by the enhancer-promoter activity of the U₃ region of the retroviral LTR. (B) The transcription of the therapeutic gene is driven by the addition of an internal promoter. The U₃ 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.