CNS targeting AAV vectors and methods of use thereof
The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders.
1. A method for delivering a transgene to CNS tissue in a subject, the method comprising: administering an effective amount of a rAAV comprising a promoter operably linked with a transgene to central nervous system (CNS) tissue by intrathecal administration, wherein the rAAV infects cells of the CNS of the subject, wherein the transgene encodes an inhibitory RNA that has the sequence of SEQ ID NO: 26, wherein the inhibitory RNA is complementary with and specifically binds to a target site sequence of the SOD1 mRNA and inhibits expression of SOD1 protein in the subject, wherein the target site sequence of the SOD1 mRNA comprises at least 5 nucleotides that are complementary with a sequence as set forth in SEQ ID NO: 26.
2. The method of claim 1 , wherein the intrathecal administration is in the lumbar region of the subject.
3. The method of claim 1 , wherein the dose of the rAAV for intrathecal administration is in a range of 10 10 genome copies to 10 14 genome copies.
4. The method of claim 1 , wherein the intrathecal administration is in the cervical region of the subject.
5. The method of claim 1 , wherein the intrathecal administration is in the thoracic region of the subject.
6. The method of claim 1 , wherein the cells of CNS tissue are oligodendrocytes, astrocytes, neurons, brain parenchyma cells, and/or Purkinje cells.
7. The method of claim 1 , wherein the inhibitory RNA is an antisense RNA, a shRNA or a miRNA.