The invention provides adeno-associated virus (AAV) replication (Rep) sequences. In one embodiment, the invention provides nucleotide sequences encoding a chimeric protein, wherein the encoded chimeric protein contains a wild type AAV Rep inhibitory amino acid sequence, and wherein the nucleotide sequences contain a scrambled and/or deoptimized polynucleotide sequence encoding the wild type AAV Rep inhibitory amino acid sequence. The invention provides vectors, cells, and viruses containing the invention's sequences. Also provided are methods for detecting portions of the AAV Rep inhibitory amino acid sequence, which reduce replication and/or infection and/or productive infection by viruses. The invention's compositions and methods are useful for site-specific integration and/or expression of heterologous sequences by recombinant adeno-associated virus (rAAV) vectors and by rAAV virus particles, such as hybrid viruses (e.g., Ad-AAV) comprising such vectors. The invention's compositions and methods find application in, for example, gene therapy and/or vaccines.

The present invention relates to methods of treating cancer in a human subject in need thereof. In particular, the present invention relates to treating a cancer by administering a recombinant virus which expresses one or more biotherapeutic agents in a subject, and administering to the subject a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent. The invention further relates to method for treating cancer by administering a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent and a caspase inhibitor, and, optionally, also administering a recombinant virus expressing one or more biotherapeutic agents in the subject. The invention also relates to a method for treating cancer by administering purified interferon gamma to a subject and administering to the subject a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent. Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions containing: a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent and a recombinant virus; a nucleotide analogue or nucleotide analogue precursor chemotherapeutic agent and a caspase inhibitor; or a purified interferon gamma and a nucleotide analogue or nucleotide precursor analogue chemotherapeutic agent.

The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.

Provided herein are adeno-associated virus (AAV) compositions that can restore phenylalanine hydroxylase (PAH) gene function in cell. Also provided are methods of use of the AAV compositions, and packaging systems for making the AAV compositions.

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

The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.

Provided herein are AAV8 mutant capsids and rAAV comprising the same. In one embodiment, vectors employing the AAV8 mutant capsid show increased transduction in a selected tissue as compared to AAV8.

An object of the present invention is to provide a conditionally replicating adenovirus having a strong anticancer effect. A conditionally replicating adenovirus to replicate specifically in a cancer cell and express REIC protein or REIC C domain protein, wherein the conditionally replicating adenovirus is obtained by inserting full-length REIC DNA or REIC C domain DNA into a conditionally replicating adenovirus comprising an ITR (inverted terminal repeat) sequence of an adenovirus type 5 genome and insertion of an HRE sequence, an hTERT promoter, a decorin-encoding DNA, and a DNA encoding a peptide comprising an RGD sequence.

The present invention relates to a composition for intracellular delivery containing an adenovirus protein VI-derived peptide and an anti-cancer pharmaceutical composition containing the same. According to the present invention, the use of the peptide or peptide-polymer composite of the present invention improves intracellular delivery efficiency of a nucleic acid, a peptide, a poly-peptide, an antibody, a chemical material, or a virus. Therefore, the peptide or peptide-polymer composite of the present invention can be favorably used as an intracellular delivery system for various therapeutics.

The present invention relates to a novel gene delivery system and recombinant adenovirus comprising the decorin-encoding sequence to enhance transduction efficiency of transgenes, a pharmaceutical anti-tumor composition comprising the recombinant adenovirus, a pharmaceutical composition having improved tissue penetration potency and a pharmaceutical composition for treating a disease or disorder associated with accumulation of excess extracellular matrix.