Interneuron-specific therapeutics for normalizing neuronal cell excitability and treating Dravet syndrome

A viral vector comprising a polynucleotide sequence including a gene of interest and an isolated enhancer polynucleotide sequence that restricts expression of the gene of interest in interneuron or neuron cells in the brain;

• wherein the isolated enhancer polynucleotide sequence of the vector comprises the polynucleotide sequence of an isolated enhancer element selected from the group consisting of:
• E1 as set forth in SEQ ID NO:
• 5 or SEQ ID NO:
• 15, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• E2 as set forth in SEQ ID NO:
• 6 or SEQ ID NO:
• 16, which restricts expression of the gene of interest in parvalbumin (PV)-expressing cortical interneurons in the brain;
• E3 as set forth in SEQ ID NO:
• 7 or SEQ ID NO:
• 17, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• E4 as set forth in SEQ ID NO:
• 8 or SEQ ID NO:
• 18, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• E5 as set forth in SEQ ID NO:
• 9 or SEQ ID NO:
• 19, which restricts expression of the gene of interest in pyramidal (PYR) cortical neurons in the brain;
• E6 as set forth in SEQ ID NO:
• 10 or SEQ ID NO:
• 20, which restricts expression of the gene of interest in vaso-intestinal peptide (VIP)-expressing cortical interneurons in the brain;
• E7 as set forth in SEQ ID NO:
• 11 or SEQ ID NO:
• 21, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• E8 as set forth in SEQ ID NO:
• 12 or SEQ ID NO:
• 22, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• E9 as set forth in SEQ ID NO:
• 13 or SEQ ID NO:
• 23, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain;
• and
• E10 as set forth in SEQ ID NO:
• 14 or SEQ ID NO:
• 24, which restricts expression of the gene of interest in GAD1-expressing cortical interneurons in the brain.