Abstract: An engineered AAV capsid is provided, in which at least one protein on the capsid is modified to include a n-mer motif, which promotes transduction of the capsid into the central nervous system (CNS). Further embodiments provide a vector system comprising one or more vectors encoding AAV capsids and a method of delivering cargo to the CNS. The method comprises administering, in vivo or in vitro, a AAV capsid according to embodiments described herein and the AVV capsid comprises one or more cargo molecules.

Abstract: Highly selective targeting moieties and compositions comprising the targeting moieties are described herein to efficiently transduce endothelial cell of the central nervous system vasculature. Embodiments include use and delivery of the targeting moieties and compositions to selectively direct delivery of cargo.

Abstract: Provided are compositions and kits comprising recombinant adeno-associated viruses (rAAVs) with tropisms showing increased specificity and efficiency of viral transduction in targeted cell-types, for e.g., the brain and the liver. Therapeutic and bio-medical research applications of the rAAVs are also described, including without limitation methods of discovering rAAVs using a multiplexed Cre recombination-based AAV targeted evolution (M-CREATE) method, and methods of treating various diseases and conditions by rAAV-mediated transgene therapy.