Selective cell death-inducing enzyme system

A fusion protein comprising

• (a) at least one variant caspase;
• (b) at least one inhibitor of anti-apoptotic proteins;
• and
• (c) a tobacco etch virus (TEV) protease,
• wherein:
• (i) the at least one variant caspase, the at least one inhibitor of anti-apoptotic proteins and the TEV protease are all separated by recognition sites for the TEV protease, so they can be released from each other upon cleavage by the TEV protease;
• (ii) the variant caspase comprises a TEV recognition site, so that upon cleavage by the TEV protease two fragments of the caspase are released,
• wherein the at least one variant caspase is selected from the group consisting of:
• variant caspase 3 having SEQ ID NO:
• 5, from which fragments of SEQ ID NOS:
• 9 and 10 are released upon cleavage by the TEV protease;
• variant caspase 7 having SEQ ID NO:
• 6, from which the fragments of SEQ ID NOs:
• 11 and 12 are released upon cleavage by the TEV protease;
• variant caspase 8 having SEQ ID NO:
• 7, from which the fragments of SEQ ID NOs:
• 13 and 14 are released upon cleavage by the TEV protease;
• and
• variant caspase 10 having SEQ ID NO:
• 8, from which the fragments of SEQ ID NOs:
• 15 and 16 are released upon cleavage by the TEV protease,
• (iii) the inhibitor of anti-apoptotic proteins is selected from the group consisting of second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) comprising SEQ ID NO:17 and X-linked inhibitor of apoptosis-associated factor-1 (XAF1) comprising SEQ ID NO:18;
• and
• (iv) the recognition sites for the TEV protease separating the at least one variant caspase, the at least one inhibitor and the TEV protease are selected from the group consisting of ENKYFQS (SEQ ID NO:
• 3) and ENLYFQG (SEQ ID NO:
• 4).