AU2024346724A1 — Therapeutic adeno-associated virus using nucleic acid encoding alpha-glucosidase (gaa) for treating pompe disease, with heterologous signal peptide

USPTO Abstract

Disclosed herein is a method for the treatment of Pompe Disease comprising administering a recombinant AAV (rAAV) vector comprising a rAAV genome comprising a heterologous nucleic acid encoding a heterologous BM40 signal peptide and an acid alpha-glucosidase (GAA) polypeptide, or N-terminal truncation thereof, where the heterologous nucleic acid is operatively linked to a liver-specific promoter, where the nucleic acid encoding GAA polypeptide can be wild type nucleic acid sequence, or modified nucleic acid sequence, or a codon optimized nucleic acid sequence, and can optionally be modified to reduce or completely eliminate CG and CpG dinucleotides and, optionally eliminated alternative reading frames (ARF) content.