Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: Methods of production and purification for viruses and virus-derived vectors, including those related to alphaviruses, are disclosed. in one aspect, methods of purification that subject alphavirus replicon particle preparations to one or more steps of chromatographic purification, such as using an ion exchange resin, are provided. Also disclosed are methods of characterizing alphavirus replicon particles and utilizing these materials for vaccines and gene-based therapeutics.

Abstract: The present invention provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems.

Abstract: Expression cassettes are provided comprising a promoter operably linked to a nucleic acid molecule which, when transcribed in vivo, forms double-stranded RNA that induces the production of interferon. Expression cassettes also are provided comprising a promoter operably linked to a ribozyme or antisense nucleic acid molecule which, when transcribed in vivo, forms a ribozyme or antisense RNA molecule that stimulates an immune response. In addition, expression cassettes are provided comprising a promoter operably linked to a ribozyme or antisense nucleic acid molecule which, when transcribed in vivo, stimulates apoptosis. Finally, gene delivery vectors are provided which contain such expression cassettes, host cells containing the gene delivery vectors, and methods of utilizing the expression cassettes, gene delivery vectors, and host cells.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: Methods are provided for generating immune responses utilizing alphavirus-based vector systems.

Abstract: The invention provides a bacterium containing a polynucleotide comprising a nucleic acid encoding a heterologous antigen, as well as fusion protein partners. Also provided are vectors for mediating site-specific recombination and vectors comprising removable antibiotic resistance genes.

Abstract: The invention provides a bacterium containing a polynucleotide comprising a nucleic acid encoding a heterologous antigen, as well as fusion protein partners. Also provided are vectors for mediating site-specific recombination and vectors comprising removable antibiotic resistance genes.

Abstract: Gene delivery vectors, such as, for example, recombinant FIV vectors, and methods of using such vectors are provided for use in treating or preventing retinal diseases of the eye and diseases of the brain associated with lysosomal storage disorders.

Abstract: The present invention provides Listeria that are attenuated for entry into non-phagocytic cells as well as a variety of methods of inducing immune responses involving administering compositions comprising the attenuated Listeria. Some of the attenuated Listeria are mutant Listeria that comprise at least one mutation in a gene encoding an invasin, such as an internalin. Some of the attenuated Listeria are further attenuated for cell-to-cell spread. Pharmaceutical compositions and vaccines useful in the methods of the invention are further provided. Methods of making and improving vaccines are also provided.

Abstract: Free-living microbes are provided in which the nucleic acid has been modified so that the microbe is attenuated for proliferation and/or which comprise genetic mutations that attenuate the ability of the microbe to repair its nucleic acid. Methods of using the modified microbes for the loading, activation, and/or maturation of antigen-presenting cells are also provided. Vaccine compositions comprising the modified microbes and/or the antigen-presenting cells and methods of using the vaccines are also provided. The microbes may be further modified to include heterologous antigens, such as tumor antigens or infectious disease antigens, for use as a vaccine against cancer or infectious diseases.

Abstract: Methods of production and purification for viruses and virus-derived vectors, including those related to alphaviruses, are disclosed. In one aspect, methods of purification that subject alphavirus replicon particle preparations to one or more steps of chromatographic purification, such as using an ion exchange resin, are provided. Also disclosed are methods of characterizing alphavirus replicon particles and utilizing these materials for vaccines and gene-based therapeutics.

Abstract: Gene delivery vectors, for example, recombinant FIV vectors, and methods of using such vectors are provided for use in treating or preventing retinal diseases of the eye and diseases of the brain associated with lysosomal storage disorders.

Abstract: The present invention provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems.

Abstract: The present invention provides compositions and methods for utilizing recombinant alphavirus vectors. Also disclosed are compositions and methods for making and utilizing eukaryotic layered vector initiation systems.

Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein gene which, when operably incorporated into a recombinant alphavirus particle, eukaryotic layered vector initiation system, or RNA vector replicon, has a reduced level of vector-specific RNA synthesis, as compared to wild-type, and the same or greater level of proteins encoded by RNA transcribed from the viral junction region promoter, as compared to a wild-type recombinant alphavirus particle. Also disclosed are RNA vector replicons, alphavirus vector constructs, and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules.

Abstract: Gene delivery vectors, such as, for example, recombinant FIV vectors, and methods of using such vectors are provided for use in treating or preventing retinal diseases of the eye and diseases of the brain associated with lysosomal storage disorders.

Abstract: Isolated nucleic acid molecules are disclosed, comprising an alphavirus nonstructural protein 2 gene which, when operably incorporated into an alphavirus replicon particle, eukaryotic layered vector initiation system, alphavirus vector construct or RNA vector replicon, provides a noncytopathic phenotype or confers the ability to establish persistent replication. Also disclosed are RNA vector replicons, alphavirus vector constructs, alphavirus replicon particles and eukaryotic layered vector initiation systems which contain the above-identified nucleic acid molecules, as well as methods of using such replicons, constructs, particles and eukaryotic layered vector initiation systems for expression of recombinant proteins.

Abstract: Disclosed are gene therapy vectors based upon the feline immunodeficiency virus, as well as related packaging cell lines, methods for production, and methods of use.

Abstract: Tissue cells of an animal transformed with a multivalent recombinant vector construct are provided. The vector construct expresses a therapeutic protein and either (a) a second protein or active portion thereof capable of inhibiting MHC antigen presentation; (b) an antisense message capable of inhibiting MHC antigen presentation; or (c) a ribozyme capable of inhibiting MHC antigen presentation. Pharmaceutical compositions comprising such multivalent constructs are also provided. The transformed tissue cells are particularly useful within methods for suppressing an immune response.