Provided herein are compositions and methods for the viral gene therapy (e.g., AAV-directed gene therapy) of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C

The present invention relates to novel adenovirus strains with a high immunogenicity and very low pre-existing immunity in the general human population. The absence of detectable neutralizing antibodies is due to novel hypervariable regions in the adenoviral capsid protein hexon. The present invention provides nucleotide and amino acid sequences of these novel adenovirus strains, as well as recombinant viruses, virus-like particles and vectors based on these strains. Further provided are pharmaceutical compositions and medical uses in the therapy or prophylaxis of a disease, and methods for producing an adenovirus or virus-like particles utilizing the novel sequences, recombinant viruses, virus-like particles and vectors.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

Producing adenovirus gene therapy vector in producer cells that express or over-express adenoviral polypeptide IX enables one to produce pIX-deleted adenovirus in suspension cell culture. Using producer cells that express or over-express adenoviral polypeptide IX also increases the yield of adenovirus vector, regardless of whether that adenovirus is pIX-deleted. Using producer cells that express or over-express adenoviral polypeptide IX also improves the resulting vector's transduction kinetics, reducing the number of pfu/target cell required to achieve a given level of transduction/infection, shortening the time the vector requires to transduce or infect a target cell, and shortening the time an infected target cell produces progeny virus.

This invention provides methods and materials for treating cancer. The invention encompasses methods and materials for delivering programmed death-ligand 1 (PD-L1) binding compounds and/or compositions containing one or more monovalent or multivalent programmed death-ligand 1 (PD-L1) binding compounds which are administered to a mammal having cancer to treat the mammal. In some cases, a multivalent PD-L1 binding compound can include two or more programmed cell death protein 1 (PD-1) polypeptides (and/or fragments thereof having the ability to bind PD-L1). This invention also provides methods and materials for making multivalent PD-L1 binding compounds and methods and materials for making nucleic acid molecules that encode PD-L1 binding compounds.

The present invention provides recombinant adenoviral compositions and methods for their use in treating disorders associated with epithelial tissues.

Provided herein is a conditionally-replicating serotype 5 adenovirus or adenoviral vector expressing a mutant E1A protein under control of a promoter that is responsive to hypoxia and inflammation and one or more immune modulators under control of a tumor-specific promoter. The adenovirus or adenoviral vector also comprises serotype 3 fiber and hexon proteins. Also provided is a method of inducing cytotoxicity in tumor cells using a composition containing the adenovirus or adenoviral vector.

The invention provides a gene sequence which can encode and express adenovirus hexon protein in vitro, and is represented as SEQ ID NO: 3. Also invented a protein which was translated and expressed by the gene sequence according to the invention, and the invention also relates to the use of the protein as an antigen to immunize rabbits to obtain a polyclonal antibody. The antibody mentioned above can detect adenovirus with high sensitivity and specificity.

The present invention relates to a cell line for producing an adenovirus having a limited autoreplication capability, and a method of preparing the same, and more particularly, to a cell line for producing an adenovirus having no autoreplication capability by expressing at least one selected from an adenoviral E1 protein and an E1A or E1B protein, and a method of preparing the same. Also, the present invention relates to the use of the cell line expressing at least one selected from the adenoviral E1 protein and the E1A or E1B protein.

The invention provides a Gene sequence which can encode and express adenovirus hexon protein in vitro, and is represented as SEQ ID NO: 3. Also invented a protein which was translated and expressed by the gene sequence according to the invention, and the invention also relates to the use of the protein as an antigen to immunize rabbits to obtain a polyclonal antibody. The antibody mentioned above can detect adenovirus with high sensitivity and specificity.