The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

An engineered polypeptide derived from adenovirus pentane base protein. The polypeptide of the invention is based on the “upper” alpha-helical domain of the adenovirus pentane base as shown in the pentane base atomic structure, but it lacks essentially completely any amino acids of the beta-barrel sheet domain showing a jellyroll fold structure (the jellyroll fold domain). The polypeptide contains at least the large fragment of the alpha-helical domain of the pentane base, which fragment includes the RGD loop(s) and the VLP loop, and may contain also the second, short fragment of the alpha-helical domain of the adenovirus pentane base. The polypeptide of the invention provides a new scaffold for optimized presentation of peptidic entities such as oligopeptides, polypeptide sequences, protein domains, proteins and protein complexes as high affinity agents to target molecules.

This invention generally relates to methods for treating or preventing the symptoms of non-alcoholic fatty liver disease, methods for reducing excessive fat from the liver, methods of improving glycemic control, and methods for treating or preventing liver dysfunction, that comprise administering a therapeutically effective amount of Adenovirus 36 E4orf1 protein or functional variant thereof.

This disclosure describes oncolytic adenovirus constructs and methods on using the constructs. Generally, the oncolytic constructs includes at least a partial deletion of E3, a heterologous polynucleotide encoding a heterologous polypeptide in place of the at least partial deletion of E3, and a cell-specific regulatory polynucleotide operationally linked to the heterologous polynucleotide.

The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and/or fiber protein.

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

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and/or fiber protein.

Provided is the use of selectively replicating oncolytic viruses in the preparation of immunostimulants for treatment of tumors and/or cancers, wherein the oncolytic viruses do not carry exogenous immunoregulatory genes.

Synthetic adenoviruses having chimeric fiber proteins and liver detargeting mutations are described. The synthetic adenovirus vectors are capable of specifically infecting cells at wound sites or in regions of damaged tissue. The synthetic adenovirus vectors also are capable of expressing transgenes, such as wound healing factors, at sites of wounded or damaged tissue. Accordingly, the described vectors can be used to detect wounded or damaged tissue, and/or to promote wound healing and regeneration of damaged tissue, such as by expression of heterologous wound healing or tissue regeneration factors.