Abstract: Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: Human somatic cells are reprogrammed to become induced pluripotent stem cells (iPS cells) by the introduction of a minicircle DNA vector. Cells of interest include adipose stem cells.

Abstract: The present invention provides minicircle nucleic acid vector formulations for use in administering to a subject, wherein the minicircle nucleic acid vectors include a polynucleotide of interest, a product hybrid sequence of a unidirectional site-specific recombinase, and are devoid of plasmid backbone bacterial DNA sequences. Also provided are methods of producing the subject formulations as well as methods for administering the minicircle nucleic acid vector formulations to a subject. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: The present invention features compositions and methods relating to tRNA-derived small RNAs (tsRNAs). Provided herein are oligonucleotide compositions that are complementary to tsRNAs, in particular leuCAGtsRNA, and methods of using the oligonucleotides for the regulation of respective tsRNA. Further provided are methods of inducing apoptosis through the inhibition of leuCAGtsRNA.

Abstract: The silencing effect of a spacer sequence, for example a bacterial backbone sequence in a plasmid or other episomal vector, on transgene expression is reversed by engineering of the spacer to include nucleosome exclusion sequences.

Abstract: Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

Abstract: Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: Described herein is a method of expanding human hepatocytes in vivo using an immunodeficient mouse which is further deficient in fumarylacetoacetate hydrolase (Fah). The method comprises transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, allowing the hepatocytes to expand and collecting the expanded human hepatocytes. The method also allows serial transplantation of the human hepatocytes into secondary, tertiary, quaternary or additional mice. Also provided are mutant mice comprising homozygous deletions or point mutations in the Fah, Rag2 and Il2rg genes.

Abstract: Compositions and methods are provided for integrating one or more genes of interest into cellular DNA without substantially disrupting the expression of the gene at the locus of integration, i.e., the target locus. These compositions and methods are useful in any in vitro or in vivo application in which it is desirable to express a gene of interest in the same spatially and temporally restricted pattern as that of a gene at a target locus while maintaining the expression of the gene at the target locus, for example, to treat disease, in the production of genetically modified organisms in agriculture, in the large scale production of proteins by cells for therapeutic, diagnostic, or research purposes, in the induction of iPS cells for therapeutic, diagnostic, or research purposes, in biological research, etc. Reagents, devices and kits thereof that find use in practicing the subject methods are also provided.

Abstract: Compositions and methods are provided for the treatment of an ischemic cardiovascular condition by providing a patient with a novel non-viral minicircle DNA vector comprising polynucleotide sequences that potentiate HIF-1 activity, including RNAi or antisense agents selective for proteins involved in HIF1 inactivation.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

Abstract: The present invention provides minicircle nucleic acid vector formulations for use in administering to a subject, wherein the minicircle nucleic acid vectors include a polynucleotide of interest, a product hybrid sequence of a unidirectional site-specific recombinase, and are devoid of plasmid backbone bacterial DNA sequences. Also provided are methods of producing the subject formulations as well as methods for administering the minicircle nucleic acid vector formulations to a subject. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: The present invention provides minicircle nucleic acid vector formulations for use in administering to a subject, wherein the minicircle nucleic acid vectors include a polynucleotide of interest, a product hybrid sequence of a unidirectional site-specific recombinase, and are devoid of plasmid backbone bacterial DNA sequences. Also provided are methods of producing the subject formulations as well as methods for administering the minicircle nucleic acid vector formulations to a subject. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications.

Abstract: The present invention relates to systems and methods for modulating gene expression and applications thereof. Provided is a novel expression system to generate RNaseZ and RNA polymerase III dependent RNAs to regulate genes and control the timing and the location of the regulation by supplying synthetic or expressed oligonucleotide antisense to a small RNA.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating a library of recombinant adeno-associated viral capsid proteins are also provided.

Abstract: Methods and compositions for expressing a gene or nucleotide sequence of interest are provided. The compositions include an expression cassette that includes a synthetic enhancer, a transthyretin promoter, and a nucleotide sequence operably under the control of the synthetic enhancer and the transthyretin promoter. The expression cassette may be used in an adeno-associated viral (AAV) vector, such as a self-complementary AAV vector.