Abstract: Disclosed herein are recombinant AAV variant (e.g., variant serotype 5 (AAV5)) capsid proteins and variant capsid protein-containing viral particles with enhanced ability to transduce adult stem cells and neurons. Viral particles containing these capsid variants are capable of enhanced transduction of mammalian mesenchymal stem cells and neurons. The recombinant AAV5 variant proteins and viral particles disclosed herein were identified from a variant AAV5 capsid library that was engineered by making substitutions in variable regions of the capsid. Compositions of these variant AAV5 particles are provided that are useful for transducing and delivering therapeutic transgenes to cells, such as mesenchymal stem cells, and thus treat diseases and disorders pertaining to these cells.

Abstract: Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in host producer cells, such as insect cells. In some embodiments, methods, uses and compositions are provided that comprise recombinant VP1 genes comprising modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles. These infective rAAV particles may comprise a gene of interest.

Abstract: Provided herein are methods and compositions useful in the screening and production of recombinant AAV (rAAV) that have structural fitness and potency in insect cells and mammalian cells. The disclosure provides a directed evolution system for generating and selecting rAAV variants based on their Kozak sequences. In some embodiments, methods disclosed herein comprise the use of modified Kozak sequences to express AAV2 VP1 proteins in amounts that are useful for producing rAAV particles having high infectivities and/or transduction efficiencies. In some embodiments, methods of producing, and methods of screening, rAAV are provided that comprise the steps of infecting insect cells by administering rAAV to these cells, recovering rAAV-integrated DNA from these insect cells, and transfecting recovered rAAV into mammalian cells. Also provided herein are nucleic acids comprising nucleotide sequences encoding novel Kozak sequences.

Abstract: Described herein are AAV particles having capsid proteins with amino acid substitutions that confer increased affinity for and transduction of glioma cells. The disclosed capsid proteins may be used in conjunction with any therapeutic transgene for treatment of cancer, including in the manufacture of an AAV particle. Also described are methods of identifying AAV variants having increased affinity for and transduction of specific tumor cell types.

Abstract: Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in insect cells. In some embodiments, methods and compositions include the use of modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles.

Abstract: Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in insect cells. In some embodiments, methods and compositions include the use of modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles.

Abstract: Provided herein are methods and compositions useful in the production of recombinant AAV (rAAV) in host producer cells, such as insect cells. In some embodiments, methods, uses and compositions are provided that comprise recombinant VP1 genes comprising modified Kozak sequences to express AAV VP1 proteins in amounts that are useful for producing infective rAAV particles. These infective rAAV particles may comprise a gene of interest.