Gene therapy construct for treating pompe disease, pharmaceutical composition, and method

A mutant promoter comprising a polynucleotide selected from the group consisting of:

• (i) a polynucleotide of SEQ ID NO:
• 4.
• (ii) a polynucleotide having at least 95%, 96%, 97%, 98%, 99%, 99.5% identity to SEQ ID NO:
• 4.
• (iii) a polynucleotide obtained by substitution, deletion or addition of one or several nucleotides to the polynucleotide of SEQ ID NO:
• 4,
• and wherein the polynucleotide has a mutation at positions 562-572 of SEQ ID NO:4 or at positions corresponding thereto, preferably said mutation is a mutation from T to C or G or A at position 568 or at a corresponding position, and more preferably a T to C mutation;
• preferably, the mutant promoter increases the expression of a gene of interest functionally linked thereto, e.g., increases by 1%-70%, such as at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, or at least 50%, at least 60%, relative to a reference promoter consisting of a corresponding polynucleotide without the mutation;
• more preferably, the mutant promoter is a constitutive promoter, wherein the mutant promoter increases the expression of the gene of interest in mammalian cells or tissues relative to the reference promoter, e.g., increases the expression of the gene of interest in mammalian peripheral tissues and/or central nervous tissues, e.g., increases the expression in mammalian tissues selected from the group consisting of the heart, the liver and/or the brain, and preferably the mammal is a human or a non-human mammal.