Abstract: The inventive vector specifically directs entry into a cell of monocytic origin. The vector is composed of a nucleic acid component, a lysosome evading component and a particle that can be phagocytized. The vector itself, or cells pretreated with the vector, are useful in all gene medicine applications. Because it is specific for monocytic cells, the inventive vector is particularly suited to vaccine applications. Due to the ability of monocytic cells to target tumors, the inventive vector also is suitable for use in anti-tumor applications, including conventional gene therapy.

Abstract: The present invention relates to compositions and methods for the selection and use of surface exposed epitopes. The present invention includes in vivo and in vitro phage peptide diplay methods for the identification and selection of peptides and peptide associated factors with desired properties (e.g., targeting specificity, stability, etc.). The present invention further provides methods and compositions for the isolation and identification of peptide-specific antibodies. The present invention also includes methods and compositions employing nuclear localization signals for enhanced nuclear transport and expression of DNA.

Abstract: The present invention relates to the field of the regulation of the expression of genes and is based in particular on the use of constructs which make it possible to activate the transcription of a transgene in cells, tissues or organs under inflammatory conditions. The promoters of the invention preferably comprise a) a PPAR response element and b) the whole or part of the promoter of the PLA2sIIA gene. The invention also relates to vectors, cells and compositions comprising these promoters, as well as their use for the regulation of the expression of genes in vitro, ex vivo or in vivo.

Abstract: Methods and vectors (both DNA and retroviral) are provided for the construction of a Library of mutated cells. The Library will preferably contain mutations in essentially all genes present in the gene of the cells. The nature of the Library and the vectors allow for methods of screening for mutations in specific genes, and for gathering nucleotide sequence data from each mutated gene to provide a database of tagged gene sequences. Such a database provides a means to access the individual mutant cell clones contained in the Library. The invention includes the described Library, methods of making the same, and vectors used to construct the Library. Methods are also provided for accessing individual parts of the Library either by sequence or by pooling and screening. The invention also provides for the generation of non-human transgenic animals which are mutant for specific genes as isolated and generated from the cells of the Library.

Abstract: The invention relates to improved E. coli bacteria with enhanced viability at low temperatures, methods for producing improved bacterial strains capable of enhanced viability at low temperatures, and the isolation and use of genetic material capable of enhancing the viability of bacteria at low temperatures. In addition to the enhanced viability at low temperatures, the bacteria may exhibit enhanced transformation efficiencies after storage at low temperatures. As such, the invention may be used for the insertion of exogenous DNA sequences into the bacteria of the invention.

Abstract: The invention relates to nucleic acid molecules comprising a heat-inducible promoter and to expression vectors and host cells containing at least one nucleic acid molecule according to the invention. The present invention further relates to kits and methods for producing one or more proteins using the nucleic acid molecules according to the invention and to various uses of the same. The object of the invention is to provide a promoter the heat-inducible characteristic of which is as selective as possible, in particular a promoter which is active in yeasts and which is suitable for protein expression at high temperatures.

Abstract: The present invention provides biodegradable polymers, polymer compositions, particles composed thereof and methods of using same for the controlled release of a biologically active substance to a specified tissue or cells. Preferred polymers include biodegradable, amphiphilic polyphosphates which are capable of complexing one or more biologically active substances. Preferred methods include the controlled release of biologically active substances and gene therapy using polymers and nanoparticles composed thereof.

Abstract: The invention provides new urothelial cell specific transcriptional regulatory sequences derived from human uroplakin II (hUPII), as well as polynucleotide constructs such as adenoviral vectors and methods of using hUPII-derived TREs. Additionally, the invention provides adenoviral vectors comprising a gene, preferably an adenovirus gene, under transcriptional control of a urothelial cell-specific transcriptional regulatory element (TRE). These vectors display urothelial cell-specific cytotoxicity, which is especially useful in the context of bladder cancer, in which destruction of these cells is desirable. The invention further provides compositions and host cells comprising the vectors, as well as method of using the adenoviral vectors.

Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme for example. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect.

Abstract: The production of recombinant gene products from cultures of the yeast Zygosaccharomyces bailii strains transformed with expression vectors bearing the gene coding for the proteins.

Abstract: Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant genetic toggle switches which contain a first constitutive promoter-regulatory gene operon and a second constitutive promoter-regulatory gene operon. Expression of the regulatory gene from the first operon inhibits expression from the promoter in the second operon, and expression of the regulatory gene from the second operon inhibits expression from the promoter in the first operon. By use of the toggle switch and various switching agents it is possible to reversibly switch the expression of a gene of interest between a stable “on” state and stable “off” state or vice versa via transient exposure to a switching agent.

Abstract: Site-specific recombinase based methods for making a recombinant adenoviral genome, as well as kits for practicing the same and the recombinant adenovirus vectors produced thereby, are provided. In the subject methods, the subject genomes are prepared from donor and acceptor vectors that each include at least one site recombinase recognition site, where in certain preferred embodiments, one of the donor and acceptor vectors includes a single recombinase recognition site while the other includes two recombinase recognition sites. The acceptor vector includes an adenoviral genome having an E region deletion. The donor vector includes an insertion nucleic acid. In the subject methods, the donor and acceptor vectors are combined in the presence of a recombinase to produce an adenoviral genome that includes the insertion nucleic acid. The subject adenoviral genomes find use in a variety of applications, including as vectors for use in a variety of applications.

Abstract: Methods and compositions for treating a congenital heart disease and methods and compositions for prognosing or diagnosing a congenital heart disease in a subject are disclosed.

Abstract: The invention provides Drosophila melanogaster p70S6K, as well as nucleic acids encoding this kinase. The sequence of Drosophila p70S6K and the gene encoding it are represented in SEQ ID No. 2 and 1 respectively. The invention moreover provides mutated forms of Drosophila p70S6K, including constitutively active and dominant negative forms thereof, which are useful in the study of p70S6K activity. Furthermore, the invention provides expression systems which produce Drosophila p70S6K in Drosophila and other organisms, and in particular systems in which expression of Drosophila p70S6K has been modulated so as to facilitate the study of its activity.

Abstract: Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant adjustable-threshold switches which contain a first inducible promoter-regulatory gene operon and a second constitutive promoter-regulatory gene operon. A threshold amount of activating agent is required to switch the inducible promoter “on” and the constitutive promoter “off”. An adjustable-threshold switch is useful to reversibly switch the expression of a gene of interest between a stable “on” state and stable “off” state in response to an activating agent at or above a threshold concentration.

Abstract: The invention provides methods and compositions relating to novel human cellular inhibitor of apoptosis proteins (c-IAP1/2) comprising a series of defined structural domain repeats and/or a RING finger domain; in particular, at least two of: a particular first domain repeat, a particular second domain repeat, and a particular third domain repeat, and/or a particular RING finger domain. The proteins provide a c-IAP specific function, with preferred proteins being capable of modulating the induction of apoptosis; for example, by binding a human tumor necrosis factor receptor associated factor (TRAF). The compositions include nucleic acids which encode the subject c-IAP and hybridization probes and primers capable of hybridizing with the disclosed c-IAP genes. The invention includes methods of using the subject compositions in therapy, in diagnosis and in the biopharmaceutical industry.

Abstract: The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signalling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.

Abstract: A simple method for modifying genes in a recombination deficient host cell is disclosed. Such modifications include generating insertions, deletions, substitutions, and/or point mutations at any chosen site in the independent origin based cloning vector. The modified gene is contained in an independent origin based cloning vector that is used to introduce a modified heterologous gene into a cell. Such a modified vector may be used in the production of a germline transmitted transgenic animal, or in gene targeting protocols in eukaryotic cells. In particular, high throughput methodology is provided for generating the modified the independent origin based cloning vectors of the present invention.

Abstract: The present invention discloses a general in vitro method for isolating proteins that bind to specific RNA regulatory elements. The method employs a lyt-lys bacteriophage display library and a host bacterial cell that has been modified so as to release minimal-to-no RNase activity in the corresponding phage lysate.

Abstract: This invention provides novel nucleotide constructs. Also provided are methods for making DNA constructs useful for introducing sequences into and disrupting the function of a gene in a cell, particularly an embryonic stem cell.