Pharmacologically induced transgene ablation system

A composition for AAV-mediated delivery of a therapeutic product having a controlled transgene expression ablation system, said composition comprising

• (a) an AAV vector containing a nucleic acid molecule comprising:
• (i) a nucleic acid sequence encoding a therapeutic product operably linked to a promoter that controls transcription;
• and
• (ii) at least one endonuclease ablation site which comprises a sequence of at least 30 nucleic acid base pairs which are specifically recognized by at least ten (10×) zinc fingers, said at least one endonuclease ablation site being located at least 5′ to the sequence encoding the therapeutic product;
• (b) at least one ablator which comprises a chimeric endonuclease comprising at least ten copies of a zinc finger domain linked to a functional endonuclease catalytic domain in operative association with a promoter, wherein transcription and/or ablation activity is induced in response to a pharmacological agent, said at least ten (10×) zinc finger domain specifically recognizing said at least about 30 base pair sequence in said at least one endonuclease ablation site and comprising at least 10 independently selected recognition helices.