Abstract: Disclosed herein is a method of determining whether a first protein is capable of physically interacting with a second protein, involving: (a) providing a host cell which contains (i) a reporter gene operably linked to a protein binding site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein including the first protein covalently bonded to a binding moiety which is capable of specifically binding to the protein binding site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the second protein covalently bonded to a gene activating moiety and being conformationally-constrained; and (b) measuring expression of the reporter gene as a measure of an interaction between the first and the second proteins. Also disclosed are methods for assaying protein interactions, and identifying antagonists and agonists of protein interactions.

Abstract: Nucleic acid molecule are provided comprising a nucleic acid sequence which encodes, in order, an alphavirus capsid, a signal peptide, and an alphavirus E1 or E2 glycoprotein. Also provided are vectors encoding such nucleic acid molecules, and use of such vectors or expression cassettes to generate recombinant alphavirus particles and alphavirus packaging cell lines. In addition, modified alphavirus vector constructs are provided that permit reduced transgene expression during vector packaging, as well as methods of using such vector constructs for the production of alphavirus vector particles.

Abstract: The present invention provides recombinant viral vectors carrying a vector construct which directs the expression of a gene product (e.g., HSVTK) that activates a compound with little or no cytotoxicity into a toxic product. Also provided are methods of destroying or inhibiting pathogenic agents in a warm blooded animal, comprising the step of administering to the animal a viral vector such as that described above, in order to inhibit or destroy the pathogenic agent.

Abstract: Environmental formaldehyde can be detected and remediated in a biological system that incorporates a bacterial cell containing suitable genetic sequences encoding a formaldehyde-inducible regulatory system. The system includes a transcriptional promoter that can be specifically induced in the presence of formaldehyde to transcribe an operably linked gene.

Abstract: This invention is directed to a compound having the formula: as defined in the detailed description. The compound may be covalently linked to a delivery agent. The invention also includes a composition which comprises the compound in association with an acceptable carrier. The invention also includes a method of cleaving an RNA target sequence which comprises contacting a target sequence with the compound as described above. Further, a method of treating a disease in man or animals associated with a particular RNA which comprises administrating to the man or animal the compound. Further, the invention also includes a diagnostic reagent which comprises the compound.

Abstract: Compounds, compositions and methods are provided for inhibiting the expression of human mdm2. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding mdm2. Methods of using these oligonucleotides for inhibition of mdm2 expression and for treatment of diseases such as cancers associated with overexpression of mdm2 are provided.

Abstract: A method for intracellular amplification of DNA is disclosed. The method includes providing a mammalian cell with a first nucleic acid sequence encoding functional adenoviral E2A and E2B gene products and with a second nucleic acid sequence encoding a linear DNA fragment to be amplified. The second nucleic acid sequence further has at least one functional adenoviral Inverted Terminal Repeat on a terminus and, in one embodiment where there is only a single ITR, a hairpin-like structure on the other terminus. This allows the linear DNA fragment to be acted upon by the adenoviral E2A and E2B gene products, thus intracellularly amplifying the linear DNA fragment, which can be extracted.

Abstract: The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention comprise oligonucleotides selected from a minimally cross-hybridizing set. Preferably, such oligonucleotides each consist of a plurality of subunits 3 to 9 nucleotides in length. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports.

Abstract: A method for transforming Schizosaccharomyces pombe which comprises integrating a vector into a chromosome of Schizosaccharomyces pombe through homologous recombination, wherein the vector has an expression cassette containing a heterologous protein structural gene and a promoter and a gene segment which induces homologous recombination of the chromosome and has lost a replication origin which functions in cells of an organism other than Schizosaccharomyces pombe required for construction of the vector.

Abstract: Nucleic acid constructs are disclosed which possess a nuclear retention signal which is linked, downstream in the reading direction, to a transgene. The nuclear retention signal can regulate the presence of the transcription product in the cell nucleus or else the intracellular transport of the transcription product.

Abstract: Nuclear matrix proteins (NMP) are useful markers in diagnosing and monitoring the stage of malignancy of a cell, and in treating cell proliferative disorders associated with the NMP.

Abstract: The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating and selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, the use of such a host cell to screen drugs. The methods include the prophylactic and therapeutic treatment of viral infection, in particular HIV infection, and, thus, are also directed to viral vaccines and the treatment of cancer, in particular cancer of viral etiology. Other methods include the use of such conditionally replicating viral vectors in gene therapy and other applications.

Abstract: The present invention relates to the utilization of conditionally replicating recombinant nucleic acid molecules rescued from the integrated state for the expression of foreign proteins. The usefulness of the system is illustrated with a conditionally replicating recombinant nucleic acid molecule encoding the adeno-associated virus (AAV) capsid proteins. The present invention also relates to methods employing and conditionally replicating recombinant nucleic acid molecules for the packaging of recombinant AAV nucleic acid molecule into AAV capsids. The present invention also relates to packaging cell lines for recombinant AAV, expressing both the AAV rep and cap-genes.

Abstract: The present invention relates to a novel in vivo assay for quantitating intravasation of cancer cells based on a highly sensitive polymerase chain reaction (PCR) utilized in combination with a chick embryo chorioallantoic membrane (CAM) assay. The assay of the invention provides a method for measuring the metastatic potential of cancer cells. The assay also provides a drug screening assay for identification of agents having anti-metastatic activity.

Abstract: Compositions and methods are provided for inhibiting the expression of human tumor necrosis factor-&agr; (TNF-&agr;). Antisense oligonucleotides targeted to nucleic acids encoding TNF-&agr; are preferred. Methods of using these oligonucleotides for inhibition of TNF-&agr; expression and for treatment of diseases, particularly inflammatory and autoimmune diseases, associated with overexpression of TNF-&agr; are provided.

Abstract: Oligodeoxynucleotides are provided which are targeted to the nucleic acids encoding receptor negative regulatory domains. In a preferred embodiment, the oligodeoxynucleotides are targeted to the EPOR negative regulatory domain. Methods of enhancing cell growth through use of the oligodeoxynucleotides are also provided.

Abstract: A method for transfecting and separating cells is disclosed. The method comprises preparing magnetic particles coated with genetic material and a cell-specific ligand, and using the particles to transfect target cells. The target cells may then be separated from the non-target cells by using a magnetic field.

Abstract: Nucleotide sequences isolated from Mycobacterium tuberculosis are disclosed. These sequences are shown to encode immunostimulatory peptides. The invention encompasses, among other things, vaccine preparations formulated using these peptides.

Abstract: The present invention provides methods for altering the integration site specificity of retrotransposons and retroviruses by modifying the integrase protein (especially via engineering its coding sequence) to include a peptide portion which interacts specifically with a protein associated with a chromosome, e.g., a transcription factor, or which interacts with a particular nucleic acid sequence. Further disclosed is a peptide portion of the integrase of Ty5 which peptide portion directs integration of Ty5 or any other retrotransposon or retrovirus into whose integrase it is included into silent chromosome regions and mutant Ty5 integrase proteins for which the insertional specificity is destroyed.

Abstract: The present invention provides nucleic acid molecules capable of binding phospholipid membranes, and more particularly RNA molecules capable of binding and forming channels in biological membranes. In this regard the present invention provides methods for screening nucleic acid molecules that bind phospholipid membranes. The present invention also provides compositions of nucleic acid molecules capable of binding phospholipid membranes, as well as methods employing these compositions to alter the permeability or detectably label phospholipid membranes.