Methods and gene therapy constructs for treating GM2 gangliosidoses

A method for enhancing β-hexosaminidase A (HexA) enzyme activity in a subject in need thereof, comprising:

• administering to the subject a therapeutically effective amount of a composition comprising
• an AAV9 vector produced by expressing a construct in a cell, wherein said construct comprises a nucleotide sequence encoding from a 5′ end to a 3′ end a first ITR, a CAG promoter, a human HEXB gene, a self-cleaving P2A linker of 57 nucleotides, a human HEXA gene, and a second ITR;
• wherein the self-cleaving P2A linker of 57 nucleotides links the HEXB gene and the HEXA gene;
• wherein the nucleotide sequence from the beginning of the first ITR through the end of the second ITR consists of nucleotides 1 to 4792 of SEQ ID NO:
• 1.