Methods for xenotopic expression of nucleus-encoded plant and protist peptides and uses thereof

A method for correcting a phenotypic deficiency in a mammal that results from a mutation in a mitochondrial peptide, comprising the steps of:

• (a) establishing the identity of the mitochondrial peptide having the mutation;
• (b) preparing a nucleic-acid construct comprising a plant or protist nucleic acid sequence encoding the peptide and, optionally, a plant or protist nucleic acid sequence encoding a mitochondrial-targeting signal, wherein the plant or protist nucleic acid sequence encoding the peptide encodes a functional peptide;
• (c) introducing the nucleic-acid construct into a mammalian cell to produce a transformed cell;
• and
• (d) expressing the nucleic-acid construct from the nucleus of the transformed cell.

A pharmaceutical composition, comprising:

• (a) a plant or protist nucleic acid sequence encoding a peptide for introduction into a mitochondrion;
• (b) optionally, a plant or protist nucleic acid sequence encoding a mitochondrial-targeting signal;
• and
• (c) a pharmaceutically-acceptable carrier.

A method for introducing a functional peptide into a mitochondrion, comprising the steps of:

• (a) preparing a nucleic-acid construct comprising a nucleic acid sequence encoding the peptide and a nucleic acid sequence encoding the mitochondrial-targeting sequence of Chlamydomonas reinhardtii ATPase 6 subunit of F0F1-ATP synthase;
• (b) introducing the nucleic-acid construct into a eukaryotic cell to produce a transformed cell, wherein the eukaryotic cell is derived from an animal, a plant, a fungus, or a protozoan;
• and
• (c) expressing the nucleic-acid construct from the nucleus of the transformed cell.