Abstract: The present disclosure relates generally to modified adeno-associated virus (AAV) from serotypes other than serotype 2, which have a viral capsid protein with a subunit 1 (VP1) sequence which is modified relative to the corresponding wildtype sequence. In particular, the modified AAVs of the disclosure comprise site-specific amino acid substitutions within the phospholipase A2 (PLA2) domain and flanking sequence relative to the corresponding wild-type sequence which improve functionality of the AAV when produced in insect cells. The present disclosure also relates to methods of producing the modified AAVs, reagents therefor, baculovirus expression systems and insect cells for producing said modified AAVs.

Abstract: The present disclosure relates to modified adeno-associated virus (AAV) delivery vectors comprising ‘silence and replace’ DNA constructs, compositions comprising same, and the use of the modified AAV and compositions to treat oculopharyngeal muscular dystrophy (OPMD) in individuals suffering from OPMD or which are predisposed thereto. In particular, the disclosure relates to AAV having a capsid protein with a modified subunit 1 (VP1) and comprising a ‘silence and replace’ DNA construct, wherein the ‘silence and replace’ DNA construct comprises (i) a DNA-directed RNAi (ddRNAi) construct encoding short hairpin microRNA (shmiR) targeting PABPN1 causative of OPMD and (ii) a PABPN1 construct encoding functional PABPN1 protein having a mRNA transcript which is not targeted by the shmiRs at (i). The present disclosure also relates to the methods of treating OPMD comprising direct injection of an AAV of the disclosure to a subject's pharyngeal muscles.

Abstract: The present disclosure relates generally to modified adeno-associated virus (AAV) from serotypes other than serotype 2, which have a viral capsid protein with a subunit 1 (VP1) sequence which is modified relative to the corresponding wildtype sequence. In particular, the modified AAVs of the disclosure comprise site-specific amino acid substitutions within the phospholipase A2 (PLA2) domain and flanking sequence relative to the corresponding wild-type sequence which improve functionality of the AAV when produced in insect cells. The present disclosure also relates to methods of producing the modified AAVs, reagents therefor, baculovirus expression systems and insect cells for producing said modified AAVs.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides multiple-promoter expression cassettes for simultaneous delivery of RNAi, preferably to mammalian cells in vivo.

Abstract: The present invention provides multiple-promoter expression cassettes for simultaneous delivery of RNAi, preferably to mammalian cells in vivo.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides compositions and methods suitable for RNAi specifically in the liver so as to treat diseases or disorders.

Abstract: The present invention provides multiple-promoter expression cassettes for simultaneous delivery of RNAi, preferably to mammalian cells in vivo.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides multiple-promoter expression cassettes for simultaneous delivery of RNAi, preferably to mammalian cells in vivo.

Abstract: The present invention provides compositions and methods suitable for expressing 1-x RNAi agents against a gene or genes in cells, tissues or organs of interest in vitro and in vivo so as to treat diseases or disorders.

Abstract: The present invention provides a complex that includes a virion having a ligand that recognizes an epitope present on an immune effector cell surface and at least a first nucleic acid encoding a first non-native antigen. The invention also provides a library including a plurality of such complexes, in which antigens of at least two of the plurality are different. Using such reagents, the invention provides a method of precipitating an immune response within an immune effector cell, wherein such a complex is delivered to the cell under conditions sufficient for the cell to mount an immune response to the antigen. When applied in vivo, the method can serve to immunize an animal from the pathogen. Moreover, using a library including a plurality of complexes, which contains at least one test antigen, the invention provides a method of assessing the antigenicity of the test antigen.

Abstract: The present invention provides a chimeric protein IX (pIX). The chimeric pIX protein has an adenoviral pIX domain and also a non-native amino acid. Where the non-native amino acid is a ligand that binds to a substrate present on the surface cells, the chimeric pIX can be used to target vectors containing such proteins to desired cell types. Thus, the invention provides vector systems including such chimeric pIX proteins as well as methods of infecting cells using such vector systems.

Abstract: The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than the chimeric adenovirus fiber protein. The nonnative amino acid sequences encodes a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.

Abstract: A recombinant adenovirus comprising a chimeric adenoviral fiber protein comprising a non-adenoviral amino acid sequence in place of or in addition to a native fiber amino acid sequence, wherein the chimeric adenoviral fiber protein comprises a trimerization domain and the non-adenoviral amino acid sequence is of a size such that folding of the chimeric adenoviral fiber protein and assembly of a complex comprising the chimeric adenoviral fiber protein and a penton base is not impeded, and an adenoviral transfer vector for the generation of such a recombinant adenovirus are provided.

Abstract: The invention provides a chimeric adenovirus fiber protein including a nonnative amino acid sequence, and a chimeric adenovirus fiber protein lacking a native amino acid receptor-binding sequence. The chimeric protein trimerizes when produced in a mammalian cell.

Abstract: The invention provides adenoviral coat proteins comprising various non-native ligands. Further, the present invention provides an adenoviral vector that elicits less reticulo-endothelial system (RES) clearance in a host animal than a corresponding wild-type adenovirus. Also provided by the invention is a system comprising a cell having a non-native cell-surface receptor and a virus having a non-native ligand, wherein the non-native ligand of the virus binds the non-native cell-surface receptor of the cell. Using this system, a virus can be propagated. Further provided by the invention is a method of controlled gene expression utilizing selectively replication competence, a method of assaying for gene function, a method of isolating a nucleic acid, and a method of identifying functionally related coding sequences. Additionally, the invention provides a cell-surface receptor, which facilitates internalization.