Genvec, Inc.

Other

Leland Stanford Junior University

Cornell Research Foundation Inc.

Benitec Biopharma Limited

Petrus W Roelvink

Imre Kovesdi

Thomas J Wickham

Joseph T Bruder

Erik S Falck-Pedersen

Jason Gall

Douglas E Brough

Mark A Kay

Duncan L McVey

David A Suhy

Micheal Hebert

Methods and compositions for expressing a gene or nucleotide sequence of interest are provided. The compositions include an expression cassette that includes a synthetic enhancer, a transthyretin promoter, and a nucleotide sequence operably under the control of the synthetic enhancer and the transthyretin promoter. The expression cassette may be used in an adeno-associated viral (AAV) vector, such as a self-complementary AAV vector.

Minigene expression cassette

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.

Antigenic complexes and methods

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.

Adenoviral capsid containing chimeric protein IX

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.

Targeting adenovirus with use of constrained peptide motifs

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.

Chimeric adenovirus fiber protein

The present invention provides a recombinant protein having an amino terminus of an adenoviral fiber protein and having a trimerization domain. A fiber incorporating such a protein exhibits reduced affinity for a native substrate than does a wild-type adenoviral fiber trimer. The present invention further provides an adenovirus incorporating the recombinant protein of the present invention.

Alternatively targeted adenovirus

Targetting adenovirus with use of constrained peptide motifs

The present invention provides a short-shafted adenoviral fiber, a recombinant adenovirus comprising a short-shafted fiber, a vector comprising a short-shafted adenoviral fiber gene, and a method of targeting attachment of a short-shafted recombinant adenovirus to a cell so as to effect entry of the short-shafted recombinant adenovirus into the cell.

Short-shafted adenoviral fiber and its use

A recombinant adenovirus comprising a chimeric fiber protein and a therapeutic gene, a method of gene therapy involving the use of such an adenovirus, and an adenoviral transfer vector for the generation of such a recombinant adenovirus are provided.

Chimeric adenoviral fiber protein and methods of using same

A method of introducing an adenovirus into a cell that comprises a particular cell surface binding site, as well as a chimeric adenovirus penton base protein and recombinant adenoviral vector comprising the chimeric adenovirus penton base protein for use in the method, are provided.

Growing community of inventors

Olney, MD, United States of America

Petrus W Roelvink