Methods and products for increasing frataxin levels and uses thereof

A method for treating Friedreich ataxia in a subject comprising administering to said subject a transcription activator-like (TAL) effector-based recombinant protein or a nucleic acid encoding said recombinant protein, said recombinant protein comprising:

• i) a TAL effector domain comprising a repeat variable domain (RVD) comprising at least 10 tandem repeat monomers and a half monomer at the C-terminal end of the RVD, each monomer corresponding to an HD, NG, NN, NI, NK or NS module consisting of the amino acid sequence set forth in SEQ ID NO:
• 65 and the half monomer being a truncated monomer consisting of the first 13 contiguous amino acids of SEQ ID NO:
• 65,
• ii) a nuclear localization signal;
• and
• iii) a transcription activation domain,
• wherein said RVD binds to a sequence within nucleotides 5-50 or 81-119 of the frataxin promoter nucleotide sequence set forth in SEQ ID NO:
• 88 of a mammalian frataxin gene comprising at least 75 repeats of GAA trinucleotides in intron 1 thereof, and wherein said recombinant protein increases frataxin expression in said cell.

A method for increasing frataxin expression in a cell comprising a frataxin gene comprising at least 75 repeats of GAA trinucleotides in intron 1 thereof, the method comprising transducing said cell with a transcription activator-like (TAL) effector-based recombinant protein or nucleic acid encoding said recombinant protein, said recombinant protein comprising:

• i) a TAL effector domain comprising a repeat variable domain (RVD) comprising at least 10 tandem repeat monomers and a half monomer at the C-terminal end of the RVD, each monomer corresponding to an HD, NG, NN, NI, NK or NS module consisting of the amino acid sequence set forth in SEQ ID NO:
• 65 and the half monomer being a truncated monomer consisting of the first 13 contiguous amino acids of SEQ ID NO:
• 65,
• ii) a nuclear localization signal;
• and
• iii) a transcription activation domain,
• wherein said RVD binds to a sequence within nucleotides 5-50 or 81-119 of the frataxin promoter nucleotide sequence set forth in SEQ ID NO:
• 88 of a mammalian frataxin gene in said cell, thereby increasing frataxin expression in said cell.