The invention provides a replication-deficient serotype 28 adenoviral vector characterized by comprising a portion of a serotype 45 adenoviral hexon protein and/or a portion of a serotype 45 fiber protein in place of the endogenous serotype 28 hexon and/or fiber protein.

A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Recombinant adenoviruses that selectively replicate in E2F deregulated tumor cells are described. The recombinant adenoviruses have a genome encoding a modified E1A protein, a modified or deleted E4orf1 protein, a modified or deleted E4orf6/7 protein, or any combination thereof, such that the recombinant adenoviruses exhibit replication defects in normal cells compared to tumor cells. In some instances, the recombinant adenovirus genomes encode additional modifications that target the recombinant adenoviruses to specific cell types, detarget the viruses from the liver, inhibit viral replication in the liver, and/or evade pre-existing neutralizing antibodies.

The present invention relates to a gene expression regulating sequence consisting of a combination of HRE, E2F and TERT, and to a gene delivery system having significantly improved selective tumor cell cytotoxicity using same, and more particularly, to a recombinant adenovirus. In addition, the present invention relates to a pharmaceutical antitumor composition comprising the recombinant adenovirus. The replication of the recombinant adenovirus of the present invention is tumor-specifically regulated by the novel gene expression regulating sequence of the present invention, thus enabling the recombinant adenovirus of the present invention to exhibit improved selective tumor cell cytotoxicity or apoptotic potential, and exhibit remarkably improved antitumor effects particularly in hypoxic conditions. In addition, the specific expression of the recombinant adenovirus in tumor cells may increase in vivo stability, and thus may induce greatly improved antitumor effects.

Disclosed are non-human mammals having a modified liver and methods of making such non-human mammals having a modified liver. The modified liver may be characterized by a non-germline, stable integration of a non-endogenous gene targeted to the liver of the non-human mammal. In certain aspects, the modified liver may have greater than at least 30% ablation of the endogenous hepatocyte population of the non-human mammal. In certain aspects, the non-human mammal may comprise at least 30% non-endogenous hepatocytes. The disclosed non-human mammals may be useful for pharmacology, drug absorption, distribution, metabolism, and excretion studies, collectively ADME and toxicology studies (ADME-tox), and/or drug screening.

Novel simian adenovirus 41 and two isolates thereof are described. Various uses of these isolates, including construction of a recombinant vector which comprises simian adenovirus 41 sequences and a heterologous gene under the control of regulatory sequences are provided. A cell line which expresses simian adenovirus 41 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

The present invention provides a method of altering the specificity of an adenovirus vector. The method involves providing an adenovirus having a capsid with a modified adenovirus hexon protein. The modified adenovirus has a capsid comprising a hexon protein with a deletion in hypervariable region 1 and/or hypervariable region 4 of the hexon and an insert of an exogenous molecule therein.

A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Novel hexon isolated from simian adenovirus serotype 19 encoded in the polynucleotide defined as SEQ ID NO: 3, hepervariable region thereof, chimeric adenovirus comprising the same, and therapeutic use thereof provides a solution to the problem of safety and effective systemic treatment for developing gene therapeutic agents using adenovirus.

The present invention provides recombinant nucleic acid expression cassetie and helper dependent adenovirus, where the expression cassettes utilize a miRNA based system for controlling expression of nucleases in helper dependent adenoviral viral producer cells, thus permitting production and use for in in vivo gene editing in CD34+ cells.