Abstract: The presently disclosed invention relates to methods of transferring large nucleic acid molecules or a genome from one cell (the donor) into heterologous host cells in the presence of a crowding agent. The method allows for greater ease and efficiency of transfer of genetic material. Introduction of the donor genetic material into the recipient host cells also allows for manipulation of the donor nucleic acid molecule or genome within the host cells. Methods disclosed herein can be used to alter donor genomes from intractable donor cells in more tractable host cells.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal.

Abstract: Methods and compositions for modifying the metabolism of a subject are provided. One embodiment provides a recombinant polypeptide having a polynucleotide-binding domain, a protein transduction domain, and a targeting domain. In a preferred embodiment, the polynucleotide-binding domain includes one or more HMG box domains.

Abstract: Conjugates for the efficient delivery of sequence-specific antisense to cells of a selected type for the inhibition of a target protein have the general formula: peptide-HBL-antisense in which the peptide is a homing peptide which directs the conjugate to cells of a particular type, antisense is an antisense oligonucleotide having a sequence selected to provide sequence-specific inhibition of the target protein, and HBL is a heterobifunctional linker having reactivity towards amino and sulfhydryl groups.

Abstract: The present disclosure relates to engineered zinc finger proteins that target genes in plants involved in fatty acid biosynthesis. Methods of using such zinc finger proteins in modulating gene expression, gene inactivation, and targeted gene modification are also provided.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: The present invention relates to a hybridoma producing an anti-methylated DNA antibody, obtained by cell fusion of an antibody-producing cell obtained from an animal immunized with an antigen containing 5?-(5-methyl-2?-deoxycytidine-3?-phospho)-2?-deoxyguanosine 3?-phosphate with a myeloma cell. The present invention also relates to a monoclonal antibody produced by the hybridoma and a method for immunoprecipitation of a methylated DNA using the antibody.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal.

Abstract: An isolated antibody produced against a donor product of an enzymatically catalyzed group transfer reaction is disclosed. In one aspect, the antibody has the ability to preferentially recognize the donor-product guanosine diphosphate (GDP), in the presence of the donor molecule guanosine triphosphate (GTP). Immunuoassays using compositions including such antibodies and kits for performing the immunoassays are also disclosed.

Abstract: An antibody microarray is described comprising a plurality of antibodies immobilized on a substrate, wherein each antibody specifically binds to a synthetic oligomer (e.g., an oligonucleotide or oligopeptide) having an organic protecting group covalently bound thereto, which antibody does not bind to that synthetic oligomer when the organic protecting group is not covalently bound thereto. Methods of making and using such antibodies are disclosed, along with cells for making such antibodies. Methods of making and using such antibody microarrays are also disclosed.

Abstract: Methods and compositions for delivering polynucleotides are provided. One embodiment provides a non-viral vector comprising a recombinant polynucleotide-binding protein comprising a protein transduction domain operably linked to a targeting signal. Methods for modifying the genome of non-nuclear organelles are also provided.

Abstract: A composition for treating a nucleic acid duplex, wherein the composition is capable of inhibiting denaturation of the duplex, characterised in that the composition comprises a ubiquitin-like protein and/or a macroglobulin. It has been found that ubiquitin-like proteins (e.g. ubiquitin, NEDD8, RAD23, etc.) and macroglobulins (eg. ?2-macroglobulin) are able to stabilise nucleic acid duplexes. A nucleic acid duplex which has been contacted with the composition of the invention can be subjected to more stringent processing conditions, with denaturation of the duplex being inhibited, than would otherwise be possible. Corresponding methods and uses are also provided.

Abstract: The present invention relates to a single-chain, multiple antigen-binding molecule with diverse variable domains of a heavy and of a light chain of an immunoglobulin, which are connected in the form of a VH-VL construct, which are in turn connected together via a peptide, and to the preparation and use thereof as pharmaceutical or diagnostic aid.

Abstract: This invention describes a method whereby human autoimmune antibodies are used as carrier compounds to deliver imaging agents and pharmaceutical drugs to the tumor in the human patient. These autoantibodies have the propensity to localize in necrotic areas of tumors but not in healthy normal tissues. By combining various pharmaceutical agents with these carrier proteins it is possible to localize these agents within the necrotic areas of tumors in cancer patients. The carrier proteins may be combined with a variety of imaging agents for detection and diagnosis of tumors, and/or with a variety of radioactive or cytotoxic compounds for cancer treatment.

Abstract: The present invention relates to the cloning, sequencing and analysing of a gene cluster encoding a modular polyketide synthase enzyme involved in the biosynthesis of the antitumor compound pederin. This novel cluster represents the first example of genes from an unculturable symbiont encoding the biosynthesis of a drug candidate.

Abstract: Compositions and methods for modulating human immunodeficiency virus (HIV) infection involving substances that inhibit the ability of high mobility box 1 (HMGB1) protein to interact with natural killer (NK) cells. Therapeutic compositions comprising antibodies and drugs, such as glycyrrhizin, which bind to HMGB1. Methods of detecting or monitoring HIV infection involving detection or quantitation of HMGB1 or antibodies specific for HMGB1 in a biological sample.

Abstract: A general immunoglobulin-target assay system is provided, in which a positive outcome (the generation of a signal) depends only on the intracellular interaction of immunoglobulin with target. This can be accomplished for many immunoglobulins expressed in yeast and/or in mammalian cells and allows the selection of immunoglobulins which are capable of functioning in an intracellular environment.

Abstract: Disclosed are specific binding agents, such as fully human antibodies, that bind to angiopoietin-2. Also disclosed are heavy chain fragments, light chain fragments, and CDRs of the antibodies, as well as methods of making and using the antibodies.

Abstract: Flt3 ligand from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding said ligand. Methods of using said reagents and diagnostic kits are also provided.

Abstract: A novel testis-specific gene expressed in human prostate cancer, designated 22P4F11, is described. Analysis of 22P4F11 mRNA expression in normal prostate, prostate tumor xenografts, and a variety of normal tissues indicates that the expression of this gene is testis specific in normal tissues. The 22P4F11 gene is also expressed in human prostate tumors, in some cases at high levels. A full length cDNA encoding 22P4F11 is provided. The 22P4F11 transcript and/or protein may represent a useful diagnostic marker and/or therapeutic target for prostate cancer.

Abstract: The present invention provides a hybridization method and kit for the detection and measurement of biological molecules. A test sample containing the biological molecules of interest is hybridized with an unlabeled or optionally a detectably-labeled complementary biomolecule to form a double-stranded hybrid immobilized to a solid phase. The immobilized hybrid may be detected with an entity which specifically recognizes an RNA:DNA hybrid, followed by analyses and quantification. Therefore, the present invention provides a method and kit to detect and measure biological molecules that is simple to use, highly specific, sensitive, and accurate for screening a plurality of biological molecules.

Abstract: The present invention relates generally to the generation and characterization of anti-CA IX monoclonal antibodies. The invention further relates to the use of such anti-CA IX antibodies in the diagnosis and treatment of disorders associated with increased activity of CA IX, in particular, tumors such as colorectal cancer, renal cell carcinoma (RCC), cervical and other cancers of epithelial origin.

Abstract: The present invention relates to methods for detecting, quantifying and high throughput screening of donor-products and the catalytic activities generating the donor-products in group-transfer reactions catalyzed by adenosine triphosphatase (ATPase) or guanine triphosphatase (GTPase). The invention further provides immunoassays, antibodies and kits that may be used to practice the methods of the invention.

Abstract: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues.

Abstract: The present invention relates to methods for detecting, quantifying and high throughput screening of donor-products and the catalytic activities generating the donor-products in group-transfer reactions. The invention further provides immunoassays, antibodies and kits that may be used to practice the methods of the invention.

Abstract: The present invention relates to antibodies, antibody conjugates, and compositions thereof, methods of antibody synthesis, and applications of antibodies useful for detecting the presence of nucleic acid molecules in vivo, such as in a clinical setting. The antibodies of the invention are also useful as screening agents which allow the selection of candidate therapeutic molecules for optimum bioavailability and/or activity, and as delivery agents for cell and tissue specific delivery of nucleic acid molecules.

Abstract: The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, Staphylococcus spp., particularly S. aureus.

Abstract: Isolated polypeptides or polypeptide chains are modified by di-tyrosine cross-linking such that the retain at least one functional activity. In one embodiment, the isolated polypeptide or polypeptide chains comprise at least one di-tyrosine cross-link, wherein at least one tyrosine of the di-tyrosine cross-link originates from a point mutation to tyrosine, and wherein the di-tyrosine cross-linked protein retains at least one function displayed by the protein in the absence of di-tyrosine cross-linking. In another embodiment, the di-tyrosine cross-linked polypeptide or polypeptide chain has enhanced stability compared to the same polypeptide or polypeptide chain in the absence of di-tyrosine cross-linking. A method for stabilization of a polypeptide or polypeptide complex, by the introduction of intra-polypeptide and/or inter-polypeptide di-tyrosine bonds, which simultaneously maintains the structure and function of the polypeptide or polypeptide complex is also described.

Abstract: Clones containing a sequence encoding a glucuronide repressor are described. The nucleotide and amino acid sequences of a repressor (gusR) are presented. A glucuronide repressor is used to control expression of a transgene, detect glucuronides in a sample, and isolate glucuronides from a sample, among other uses.

Abstract: A monoclonal antibody which reacts strongly with uracil and thymine but scarcely with N-carbamyl-?-alanine; a hybridoma producing this monoclonal antibody; a method of immunochemically assaying uracil or thymine characterized by using the above-described monoclonal antibody; and diagnostics for DPD deficiency containing the above monoclonal antibody. Because of high sensitivity and specific reaction with uracil and thymine, the above-described monoclonal antibody enables convenient, quick, and selective assaying of uracil and thymine in a sample. The antibody is useful in screening patients with DPD deficient cancer with contraindication to the administration of pyrimidine fluoride-based antitumor agents.

Abstract: An artificial mammalian chromosome, more specifically, a clone containing a mammalian centromere sequence and a DNA replication origin with mammalian telomere sequences added to both ends of the clone, is provided by preparing a CEPH artificial yeast chromosome library containing a human genome, identifying clones having a repetitive human alphoid sequence from this library, and further preparing a yeast strain in which mammalian telomere sequences are added to the ends of its chromosome.

Abstract: Specific binding members, based on the third CDR of the antibody NHS76 (SEQ ID NO: 2) are provided, together with their use in methods of treatment and diagnosis.

Abstract: The present invention relates to methods and compositions for regulating the activity of imidazoline receptors. In particular, the invention relates to pharmaceutical compositions comprising imidazoleacetic acid-ribotide (IAA-RP), imidazoleacetic acid-riboside (IAA-R) and its related congeners such as pros-linked ribotide and riboside. The invention is based on the discovery that IAA-RP and to a lesser extent IAA-P bind with a high affinity to imidazoline receptors. Antibodies to IAA-RP, IAA-R are additionally provided, as well as screening methods for identification of compounds that either promote or antagonize the activity of IAA-RP, IAA-R and its related congeners. The invention further relates to diagnostic and prognostic methods for detection of abnormalities in levels or activity of IAA-RP and IAA-R. The invention encompasses treatment of disorders related to the imidazoline system, including hypertension, glaucoma, psychiatric (e.g., depression), neurological (e.g.

Abstract: The present invention provides polypeptides having pyrimidine glycosylase activity, preferably, pyrimidine glycosylase/AP lyase activity. The polypeptides include a targeting sequence, preferably an exogenous target sequence. The invention includes polynucleotides that include a coding sequence encoding the polypeptides of the present invention. Also provided by the invention are methods of using the polypeptides.

Abstract: An artificial mammalian chromosome, more specifically, a clone containing a mammalian centromere sequence and a DNA replication origin with mammalian telomere sequences added to both ends of the clone, is provided by preparing a CEPH artificial yeast chromosome library containing a human genome, identifying clones having a repetitive human alphoid sequence from this library, and further preparing a yeast strain in which mammalian telomere sequences are added to the ends of its chromosome.

Abstract: The present invention provides a hybridization method and kit for the detection and measurement of biological molecules. A test sample containing the biological molecules of interest is hybridized with an unlabeled or optionally a detectably labeled complementary biomolecule to form a double-stranded hybrid immobilized to a solid phase. The immobilized hybrid may be detected with an entity which specifically recognizes an RNA:DNA hybrid, followed by analyses and quantification. Therefore, the present invention provides a method and kit to detect and measure biological molecules that is simple to use, highly specific, sensitive, and accurate for screening a plurality of biological molecules.

Abstract: A fragment of vesicular stomatitis virus (VSV) matrix protein (M protein) and M proteins of other viral species that can inhibit nucleocytoplasmic transport of RNA, proteins and RNA-protein complexes are disclosed. These polypeptide products and related polypeptides can be used to inhibit nucleocytoplasmic transport. Further disclosed are fragments of the VSV M protein that can enter into the nucleus of a cell. These fragments and the full length of the VSV M protein can be used to introduce other polypeptides into the nucleus of a cell.

Abstract: The invention provides monoclonal antibodies to human cytochrome P450 2C8, 2C9, 2C18, and 2C19 having advantageous properties, including capacity substantially to inhibit enzyme activity of the various human cytochrome P450 2C family members and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful inter alia in methods for screening drugs for metabolism by cytochrome P450 2C family members, and in methods of screening individuals for a poor metabolizing individual human P450 2C family phenotypes.

Abstract: A product for coupling a biologically active principle with an immunovector, characterized in that the immunovector is capable of enabling the biologically active principle to be internalized into eukaryotic cells, and in that said immunovector has an affinity for the cell DNA to such an extent that it can transfer the biologically active principle into or to the immediate vicinity of the cell nuclei.

Abstract: The proliferation of uterine fibroid leiomyoma cells is inhibited by certain Fibroid Cell Growth Inhibitor (FGI) agents. The pharmacological doses of these FGI agents in the milieu of uterine fibroid cells can be made high enough to not only inhibit proliferation, but to also causes cell death. Non-invasive or minimally invasive, non-systemic delivery methods are used to deliver the FGI agent to the milieu of the target fibroid leiomyoma cell population, thereby avoiding the disadvantages and side effects of surgical and systemic hormonal therapy interventions in the treatment of uterine fibroids. The FGI agents are substrates that are normally present or are well tolerated in the human body. The efficacy of the FGI agents appears to be related to their ability to moderate the Protein Kinase C and Mitogen Activated Protein Kinase pathways. Specific FGI agents shown to be useful to inhibit growth or proliferation of uterine fibroid cells include: &agr;-tocopherol, &agr;-tocopherol succinate, and troglitazone.

Abstract: The present invention is directed to the discovery of antibodies that will react to proteins or nucleic acids bound to particular crosslinkers, but not to the free crosslinkers or free proteins or nucleic acids. Monoclonal antibodies with such binding specificity have widespread applications in receptor-ligand binding, immunodiagnostic and nucleic acid diagnostics.

Abstract: HNF-4 (hepatocyte nuclear factor 4) is a protein enriched in liver extracts that binds to sites required for the transcription of the transthyretin (TTR) and apolipoprotein CIII (apoCIII) genes (Costa et al., 1989; Costa et al., 1990; Leff et al., 1989). We have purified HNF-4 protein (54 kD) and isolated a cDNA clone encoding the protein. HNF-4 is a member of the steroid hormone receptor superfamily with an unusual amino acid in the conserved “knuckle” of the first zinc finger (DGCKG). This and the fact that HNF-4 does not bind significantly to estrogen, thyroid hormone or glucocorticoid response elements indicate that HNF-4 may represent a new subfamily. HNF-4 binds to its recognition site as a dimer and activates transcription in a sequence-specific fashion in nonhepatic (HeLa) cells. HNF-4 mRNA is present in kidney and intestine as well as liver but is absent in other tissues.

Abstract: The present invention is directed to a method of prognosticating the illness development of patients with carcinoma of the breast and/or for diagnosing carcinoma of the breast, the method comprising a qualitative determination of T1 protein and/or T1-mRNA in a sample material obtained from the patient. The invention further pertains to kits for performing the methods according to the invention.

Abstract: The invention provides a human testin (HTES) and polynucleotides which identify and encode HTES. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of HTES.

Abstract: Nutritional solutions and methods of making same are disclosed. The solutions include protein, lipid, and a carbohydrate source including high amylose starch and guar gum.

Abstract: An isolated DNA molecule encoding a Sox-9 gene which codes for the Sox-9 polypeptide. The human Sox-9 gene has been mapped to chromosome 17 in the same region as CMPD-1, the locus for Campomelic Dysplasia (CD). Sox-9 appears to have a role in mammalian skeletal development, and is used in the treatment of diseases involving bone or cartilage deficiency.

Abstract: The present invention provides methods for use in identifying, analyzing and typing polymorphic DNA fragments, particularly minisatellite, microsatellite or STR DNA fragments. In particular, the invention provides methods using DNA polymerases, more particularly thermostable DNA polymerases, and most particularly Thermotoga polymerases or mutants or derivatives thereof, whereby minisatellite, microsatellite or STR DNA molecules maybe amplified and analyzed for polymorphisms. The invention also relates to polymerases having reduced, substantially reduced or eliminated ability to add non-template 3′ nucleotides to a synthesized nucleic acid molecule. In accordance with the invention, such reduction or elimination may be accomplished by modifying or mutating the desired polymerase.

Abstract: The invention relates to the X-ray crystal structure of the hepatitis C virus helicase domain. More specifically, the invention relates to crystallized complexes of HCV helicase and an oligonucleotide, to crystallizable compositions of HCV helicase and an oligonucleotide and to methods of crystallizing an HCV helicase-oligonucleotide complex. The invention further relates to a computer programmed with the structure coordinates of the HCV helicase oligonucleotide binding pocket or the HCV helicase nucleotide triphosphate pocket wherein said computer is capable of displaying a three-dimensional representation of that binding pocket.