Abstract: Disclosed herein are novel methods for administration of rAAV particles having enhanced transduction properties, comprising the pre-incubation and co-administration of AAV capsids and polyvinyl alcohol (PVA). The disclosed methods of rAAV particle administration have improved efficiency in transducing mammalian liver and hematopoetic cells in vivo. The disclosed methods are suitable for use with a variety of AAV capsid serotypes and presudotypes and improve vector potency, thus lowering the concentration of rAAV particle required to achieve the desired effect. Further disclosed herein are buffers for storage and manufacturing of rAAV particles comprising PVA.

Abstract: Provided herein are modified AAV capsid proteins, particles, nucleic acid vectors, and compositions thereof, as well as methods of their use.

Abstract: Provided herein are recombinant adeno-associated virus (rAAV) particles encoding microRNAs targeting the glucocorticoid receptor (GR) pathway, and in particular a microRNA17-92 (miR 17-92) cluster, and genes of interest. The modified genomes of these rAAV particles comprise heterologous nucleic acid sequences encoding microRNA structures. These particles exhibit enhanced transduction efficiencies in mammalian cells. Also provided herein are compositions of nucleic acids encoding the miR 17-92 cluster and nucleic acids encoding a gene of interest. Further provided herein are methods for administering these nucleic acid compositions to enhance transduction efficiencies.

Abstract: Provided herein are compositions of recombinant adeno-associated virus (rAAV) particles capable of dampening the humoral immune response against rAAV in the host into which the rAAV particles are introduced. The modified genomes of these rAAV particles comprise heterologous insert nucleic acid and/or inverted terminal repeat (ITR) sequences containing one or more sequences associated with the human leukocyte antigen gene complex DR (HLA-DR) promoter. Also provided herein are methods for transducing host cells with modified rAAV particles to induce a dampened humoral immune responses in order to improve transduction efficiencies. Also provided herein are complexes comprising a modified rAAV particle and a Regulatory Factor X (RFX) transcription factor.

Abstract: The present invention identifies a protein, designated the D-sequence-binding protein (D-BP), is phosphorylated at tyrosine residues and blocks AAV-mediated transgene expression in infected cells by inhibiting the leading strand viral DNA synthesis. More particularly, the present invention demonstrates that D-BP is phosphorylated by EGF-R protein tyrosine kinase. Methods of increasing transcription and promoting replication of transgenes exploiting this information are disclosed herein.