Abstract: Disclosed herein are compositions and methods for treating obesity involving satiation gut peptide administration to the mouth of a subject for a predetermined dose and frequency. In other embodiments, materials and methods of treating certain psychological disorders are disclosed involving satiation gut peptides. In exemplary embodiments, the satiation gut peptide pertains to PYY.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations containing them. Also provided are methods of preparing and using the disclosed capsid-protein-mutated rAAV constructs in a variety of diagnostic and therapeutic modalities, including, inter alia, as mammalian cell-targeting delivery agents, and as human gene therapy vectors. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Production of clinical grade gene therapy vectors for human trials remains a major hurdle in advancing cures for a number of otherwise incurable diseases. Disclosed herein are systems based on a stably trans formed insect cell lines harboring helper genes required for vector production. Specifically exemplified are system embodiments that take advantage of DNA regulatory elements from two unrelated viruses—AcMNPV and AA V2. System embodiments utilize rep and/or cap genes either stably transfected in cell lines or which are introduced into cells as an expression cassette in a vector. Rep and cap genes that are designed to remain silent until the cell is infected with a viral vector. Infection with viral initiates rescue/amplification of integrated AAV helper genes resulting in dramatic induction of the expression and assembly of rAAV. The arrangement of this specific embodiment provides high levels of Rep and Cap proteins in every cell thus improving rAAV yields by 10-fold.

Abstract: Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using novel capsid-protein-mutated rAAV vector constructs in a variety of diagnostic and therapeutic applications including, inter alia, as delivery agents for diagnosis, treatment, or amelioration of one or more symptoms of disease or abnormal conditions via in situ and/or ex vivo mammalian gene therapy methods. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Production of clinical grade gene therapy vectors for human trials remains a major hurdle in advancing cures for a number of otherwise incurable diseases. Disclosed herein are systems based on a stably trans formed insect cell lines harboring helper genes required for vector production. Specifically exemplified are system embodiments that take advantage of DNA regulatory elements from two unrelated viruses—AcMNPV and AA V2. System embodiments utilize rep and/or cap genes either stably transfected in cell lines or which are introduced into cells as an expression cassette in a vector. Rep and cap genes that are designed to remain silent until the cell is infected with a viral vector. Infection with viral initiates rescue/amplification of integrated AAV helper genes resulting in dramatic induction of the expression and assembly of rAAV. The arrangement of this specific embodiment provides high levels of Rep and Cap proteins in every cell thus improving rAAV yields by 10-fold.

Abstract: Disclosed herein are compositions and methods for treating obesity involving satiation gut peptide administration to the mouth of a subject for a predetermined dose and frequency. In other embodiments, materials and methods of treating certain psychological disorders are disclosed involving satiation gut peptides. In exemplary embodiments, the satiation gut peptide pertains to PYY.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: Libraries of modified AAV cap genes are generated by synthesizing modified cap genes using degenerate oligonucleotides. Combinatorial libraries of virions composed of modified (e.g., chimeric), replication-competent AAV vectors and modified Cap proteins are also produced. Helper vectors are described that encode AAV Rep protein, modified Cap proteins, and Ad proteins. The helper vectors are used to produce stocks of virions composed of modified (e.g., chimeric) capsids and rAAV vectors.

Abstract: Adiponectin cDNA was cloned into AAV serotypes 1, 2, and 5-based expression vectors. Virions containing these vectors were administered to the livers of rat subjects via portal vein injection. A single injection of 6×1011 virions of the vector caused a sustained and statistically significant reduction in body weight of the treated animals compared to the control animals. This occurred in the absence of side effects. Compared to control animals, the subject rats also exhibited reduced adipose tissue mass, reduced appetite, improved insulin sensitivity, and improved glucose tolerance.

Abstract: Vectors that encode Adeno-Associated Virus (AAV) Rep and Cap proteins of different serotypes and Adenovirus transcription products that provide helper functions were used to produce pseudotyped recombinant AAV (rAAV) virions. Purification methods generated pseudotyped rAAV virion stocks that were 99% pure with titers of 1×1012–1×1013 vector genomes/ml.

Abstract: The invention provides modifications to a baculovirus-based recombinant adeno associated virus (AAV) system including enhancement of the helper virus stability and construction of novel baculovirus vectors for rAAV pseudotyping. The modified system extends the flexibility of rAAV vector production and promotes the utility of AAV as, a clinically applicable gene therapy vector.

Abstract: Disclosed are serotype-specific recombinant adeno-associated viral (rAAV) vectors, as well as viral particles and compositions comprising them, useful in the expression of neurotherapeutic agents (including neurotherapeutic peptides and polypeptides) in selected mammalian neural cells, as well as tissues and organ systems comprising them. In particular embodiments, rAAV serotype 1 and serotype 5 vectors are disclosed useful for the delivery of therapeutic agents to neural cells of affected mammals.

Abstract: Adiponectin cDNA was cloned into AAV serotypes 1, 2, and 5-based expression vectors. Virions containing these vectors were administered to the livers of rat subjects via portal vein injection. A single injection of 6×1011 virions of the vector caused a sustained and statistically significant reduction in body weight of the treated animals compared to the control animals. This occurred in the absence of side effects. Compared to control animals, the subject rats also exhibited reduced adipose tissue mass, reduced appetite, improved insulin sensitivity, and improved glucose tolerance.

Abstract: Vectors that encode Adeno-Associated Virus (AAV) Rep and Cap proteins of different serotypes and Adenovirus transcription products that provide helper functions were used to produce pseudotyped recombinant AAV (rAAV) virions. Purification methods generated pseudotyped rAAV virion stocks that were 99% pure with titers of 1×1012-1×1013 vector genomes/ml.

Abstract: Libraries of modified AAV cap genes are generated by synthesizing modified cap genes using degenerate oligonucleotides. Combinatorial libraries of virions composed of modified (e.g., chimeric), replication-competent AAV vectors and modified Cap proteins are also produced. Helper vectors are described that encode AAV Rep protein, modified Cap proteins, and Ad proteins. The helper vectors are used to produce stocks of virions composed of modified (e.g., chimeric) capsids and rAAV vectors.

Abstract: Disclosed are HSV-1 amplicons that supply all necessary helper functions required for rAAV packaging and methods for their use. These HSV-1 amplicons have been shown to be capable of rescuing and replicating all forms of rAAV genomes including rAAV genomes introduced into cells by infection of rAAV virions, rAAV genomes transfected into cells on plasmids or proviral rAAV genomes integrated into cellular chromosomal DNA. Also provided are methods for preparing high-titer rAAV vector compositions suitable for gene therapy and the delivery of exogenous polynucleotides to selected host cells.