Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders

A recombinant adenovirus associated (AAV) vector comprising in its genome:

• a. 5′ and 3′ AAV inverted terminal repeats (ITR) sequences, and
• b. located between the 5′ and 3′ ITRs, a heterologous nucleic acid sequence encoding a polypeptide comprising an alpha-glucosidase (GAA) polypeptide, wherein the heterologous nucleic acid is operatively linked to a liver-specific promoter selected from any one of:
• i. CRM_SP0412 (SEQ ID NO:
• 86) or SP0412 (SEQ ID NO:
• 91) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 86 or SEQ ID NO:
• 91,
• ii. SP0422 (SEQ ID NO:
• 92) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 92,
• iii. CRM_SP0239 (SEQ ID NO:
• 87) or SP0239 (SEQ ID NO:
• 93) or SP0238-UTR (SEQ ID NO:
• 147) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 87, SEQ ID NO:
• 93 or SEQ ID NO:
• 147;
• iv. CRM_SP0265 (SP0131_A1) (SEQ ID NO:
• 88) or SP0265 (LVR_SP0131_A1) (SEQ ID NO:
• 94) or SP0265-UTR (SEQ ID NO:
• 146) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 88, SEQ ID NO:
• 94 or SEQ ID NO:
• 146;
• v. CRM_SP0240 (SEQ ID NO:
• 89) or SP0240 (SEQ ID NO:
• 95) or SP0240-UTR (SEQ ID NO:
• 148) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 89, SEQ ID NO:
• 95 or SEQ ID NO:
• 148;
• vi. CRM_SP0246 (SEQ ID NO:
• 90) or SP0246 (SEQ ID NO:
• 96) or SP0246-UTR (SEQ ID NO:
• 149) or a functional variant or functional fragment thereof having at least 60% activity to SEQ ID NO:
• 90, SEQ ID NO:
• 96 or SEQ ID NO:
• 149.