Provided herein are compositions, methods and uses that relate to an easy, accurate and reliable dual or duplex assay that determines both protein and nucleic acid amounts in a viral preparation in a single container and further determines full versus empty virion content.

The present invention provides methods of generating a recombinant AAV vector with reduced immunogenicity, comprising: providing eukaryotic cells with a nucleic acid comprising a sequence of interest that is flanked by AAV inverted terminal repeats, wherein the nucleic acid comprises CpG dinucleotide sites, wherein at least a portion of the CpG dinucleotide sites are methylated, wherein the eukaryotic cell expresses one or more other components necessary to achieve recombinant AAV biosynthesis, whereby the recombinant AAV vector is generated by the eukaryotic cell, wherein the generated recombinant AAV vector comprises nucleic acid wherein at least a portion of the CpG dinucleotide sites are methylated.

A method for preparing a modified vector and a method for modifying a vector, the methods including: binding a functional group (A) in a linker compound to a functional group in a vector, wherein the functional group (A) is capable of binding to the functional group, the linker compound includes the functional group (A) and a functional group (B), and the functional group (B) is capable of binding to a ligand compound; and binding a functional group (C) in the ligand compound to the functional group (B), wherein the functional group (C) is capable of binding to the functional group (B) and the ligand compound includes the functional group (C).

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. Further provided herein are mammalian cells, baculovirus particles and insect cells comprising these nucleic acids.

A recombinant P5 promoter having an insertion of an exogenous spacer between the REP binding site and a transcription start site-localized Ying-Yang 1 (YY1) binding site is described, wherein said recombinant P5 promoter provides for a reduction in DNA contamination upstream of the P5 promoter without a concomitant reduction in viral titer.

The present invention includes methods and compositions for the production of high titer recombinant Adeno-Associated Virus (rAAV) in a variety of mammalian cells. The disclosed rAAV are useful in gene therapy applications. Disclosed methods based on co-infection of cells with two or more replication-defective recombinant herpes virus (rHSV) vectors are suitable for high-titer, large-scale production of infectious rAAV.

The invention relates to chimeric AAV capsids targeted to the central nervous system, virus vectors comprising the same, and methods of using the vectors to target the central nervous system. The invention further relates to chimeric AAV capsids targeted to oligodendrocytes, virus vectors comprising the same, and methods of using the vectors to target oligodendrocytes.

The present invention is directed to viral vectors and methods of their production and use.

This invention presents a sequence of the virus AAV/XBP1s-HA, method and its use in the improvement of cognitive functions, of memory and of learning, as presented in the in vivo studies in FIG. 12/17 right panel.

The present invention relates to variant AAV capsid polypeptides, wherein the variant capsid polypeptides exhibit an enhanced neutralization profile, increased transduction and/or tropism in human liver tissue or hepatocyte cells (i.e., human hepatocyte cells), or both, as compared non-variant parent capsid polypeptides.