Pharmacologically induced transgene ablation system

A composition for AAV-mediated delivery of a therapeutic product, said composition comprising:

• (a) a first recombinant 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 of the therapeutic product;
• and
• (ii) at least one endonuclease ablation site which comprises a sequence of at least 30nucleic 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;
• and
• (b) a second recombinant AAV vector containing the coding sequence for at least one ablator which is 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 of the at least one ablator and/or ablation activity is induced in response to a pharmacological agent and said ablator recognizes at least one endonuclease ablation site in the first recombinant AAV vector;
• wherein the nucleic acid sequence in (a)(i) consists of at least one endonuclease ablation site on the first strand of the nucleic acid sequence and at least one second endonuclease ablation is located on the second strand of the nucleic acid sequence, wherein said second endonuclease ablation site is distinct from said endonuclease ablation site on the first strand and is specifically and selectively recognized by different zinc fingers.