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.

Adeno-associated virus rh.20 sequences, vectors containing same, and methods of use are provided.

Adeno-associated virus rh.10 sequences, vectors containing same, and methods of use are provided.

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.

The disclosure provides adeno-associated virus (AAV) helper plasmid variants with improved safety profiles. In certain aspects, an AAV helper plasmid variant of the disclosure comprises one or more inactivating mutations in at least one of the following adenovirus genes or genome sequences: (a) adenoviral fiber gene; (b) adenoviral precursor terminal protein gene; (c) adenoviral L1-52K gene; (d) adenoviral 100K gene; (e) adenoviral PVIII gene; (f) adenoviral E4 region open reding frame; (g) adenoviral inverted terminal repeat (ITR) sequence; (h) L3-23K region gene; (i) hexon-assembly gene; or (j) a combination of any of (a)-(i).