RAAV-based compositions and methods for treating amyotrophic lateral sclerosis
The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.
1. A method of inhibiting expression of C9orf72 in a subject in need thereof, the method comprising administering to the subject an effective amount of a synthetic miRNA that targets a C9orf72 RNA transcript, wherein the synthetic miRNA specifically binds to a nucleic acid sequence of the RNA transcript, wherein the nucleic acid sequence of the RNA transcript bound by the synthetic miRNA is encoded by a nucleic acid sequence set forth in SEQ ID NO: 2, 6, or 7.
2. The method of claim 1 , wherein the synthetic miRNA further comprises flanking regions of miR-155.
3. The method of claim 2 , wherein the RNA transcript is a pre-mRNA transcript.
4. The method of claim 2 , wherein the RNA transcript comprises a G 4 C 2 hexanucleotide repeat.
5. The method of claim 3 , wherein the pre-mRNA transcript is a C9orf72 V 1 isoform transcript.
6. The method of claim 3 , wherein the pre-mRNA transcript is a C9orf72 V 3 isoform transcript.
7. The method of claim 3 , wherein the pre-mRNA transcript is not a C9orf72 V 2 isoform transcript.
8. The method of claim 1 , wherein the RNA transcript comprises an intron.