Protease inhibitor: protease sensitive expression system and method improving the therapeutic activity and specificity of proteins and phage and phagemids delivered by bacteria

A secreted chimeric protease inhibitor peptide, comprising a fusion of:

• a protease inhibitor peptide sequence configured to selectively inhibit a protease;
• a therapeutic peptide sequence comprising a protease cleavage site peptide sequence inhibited by the protease inhibitor peptide sequence;
• a targeting functionality peptide sequence;
• and a terminal cellular secretion signal peptide sequence,
• configured to selectively cause a cell to secrete the chimeric protease inhibitor peptide outside of the cell and inhibit cleavage of the protease cleavage site peptide sequence by the protease inhibited by the protease inhibitor peptide sequence.

A secreted chimeric protease inhibitor peptide having a plurality of fused portions, comprising:

• a terminal cellular secretion signal peptide sequence first fused portion, configured to selectively cause a cell to secrete the chimeric protease inhibitor peptide comprising the terminal cellular secretion signal peptide sequence outside of the cell;
• a protease inhibitor peptide sequence second fused portion configured to selectively inhibit a protease;
• a toxic functionality peptide sequence third fused portion comprising a protease cleavage site peptide sequence portion configured to be cleaved by the protease;
• and
• a targeting functionality peptide sequence fourth fused portion.