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 treating Canavan disease in a subject, the method comprising:
intrathecally, intraventricularly, or intravascularly administering rAAV to the subject in an amount effective for transducing oligodendrocytes of the subject with the rAAV, wherein the rAAV comprises
(i) a capsid protein having the amino acid sequence of SEQ ID NO: 9 and
(ii) a nucleic acid comprising a promoter operably linked with a region encoding aspartoacylase (ASPA), wherein the ASPA is expressed from the nucleic acid in oligodendrocytes transduced by the rAAV.
2. The method of claim 1 , wherein the nucleic acid expresses an aspartoacylase (ASPA) mRNA comprising one or more miRNA binding sites for one or more miRNAs that are more abundant in one or more non-CNS tissues in comparison to a CNS tissue.
3. The method of claim 2 , wherein the one or more miRNAs that are more abundant in one or more non-CNS tissues in comparison to the CNS tissue are at least twofold more abundant.
4. The method of claim 2 , wherein the one or more non-CNS tissue is not kidney tissue or retinal tissue.
5. The method of claim 1 further comprising evaluating kidney function in the subject at least once after the administration.
6. The method of claim 1 further comprising evaluating vision of the subject at least once after the administration.
7. The method of claim 1 , wherein the rAAV is administered intrathecally to the subject.
8. The method of claim 1 , wherein the rAAV is administered intraventricularly to the subject.
9. The method of claim 1 , wherein the rAAV is administered intravascularly to the subject.