Compositions and methods of treating Huntington's disease

An adeno-associated viral (AAV) genome comprising a first inverted terminal repeat (ITR), a promoter operably linked to a nucleic acid comprising a modulatory polynucleotide encoding a sense strand sequence and an antisense strand sequence, and a second ITR;

• wherein the encoded antisense strand sequence comprises the nucleotide sequence of SEQ ID NO:
• 918 and the sense strand sequence comprises the nucleotide sequence of SEQ ID NO:
• 1079;
• and wherein the AAV viral genome comprises one or more of:
• (i) a first ITR sequence comprising the nucleotide sequence of any one of SEQ ID NOs:
• 1380 or 1381-1383;
• (ii) a promoter comprising a chicken β-actin (CBA) promoter, a cytomegalovirus (CMV) promoter, a phosphoglycerate kinase 1 (PGK) promoter, an H1 promoter, a T7 promoter, a ubiquitin c (UBC) promoter, a β-glucuronidase (GUSB) promoter, a neuron-specific enolase (NSE) promoter, a synapsin promoter, a methyl-CpG binding protein 2 (MeCP2) promoter, or a glial fibrillary acidic protein (GFAP) promoter;
• (iii) a promoter comprising the nucleotide sequence of any one of SEQ ID NOs:
• 1410, 1411-1414;
• or
• (iv) a second ITR sequence comprising the nucleotide sequence of any one of SEQ ID NOs:
• 1382, 1380, 1381, or 1383.