The Invention

Peroxisomal enzymes are directed to the peroxisome by virtue of targeting signals that are recognized by certain receptor molecules in the cytosol of the cell. Most peroxisomal enzymes, including the oxidases, contain a Peroxisomal Targeting Signal type 1 (PTS1), which is the three amino acid sequence, serine-lysine-leucine (SKL) located at their (carboxy-terminal) end. However, the antioxidant enzyme, catalase, contains a substantially different signal from such oxidases, namely lysine-alanine- asparagine-leucine (KANL) at its carboxy terminus. All PTS1 enzymes, including the SKL-containing oxidases, as well as the KANL-containing catalase enzyme, are recognized and ferried to the organelle by the import receptor, Pex5p. By modifying catalase to contain the SKL, rather than the KANL targeting signal, efficient import of this critical enzyme is restored. Without the SKL targeting signal, catalase-deficient peroxisomes of older or disease cells continue to produce excess ROS, contributing to destruction of the cell and eventually, of the organism itself. Because of the SKL targeting signal, Catalase-SKL is imported into the peroxisome with an efficiency comparable to that of the hydrogen peroxide-producing oxidases. Importantly, EXT’s technologies do not rely on simply over-producing cellular catalase, a process that has been shown in several studies might be more harmful than beneficial. Instead, EXT’s technologies deliver genetically engineered Catalase-SKL to the cytosol of cells, and then efficiently target the molecule to peroxisomes. Once there, an oxidative balance is reestablished and excess hydrogen peroxide or other ROS are no longer produced.