Abstract: Provided is a composition comprising an analyte bound covalently or through a first binding pair to a polymer. In this composition, the analyte is less than about 2000 MW; the polymer further comprises more than one signal or first member of a second binding pair; and the analyte is not a member of the first binding pair or the second binding pair. Also provided is an assay for an analyte. The assay comprises: combining a sample suspected of containing the analyte with the above-described composition and a binding agent that binds to the analyte; and detecting the signal or the first member of the second binding pair that is bound to the binding agent. In this assay, the amount of the signal or the first member of the second binding pair bound to the binding agent is inversely proportional to the analyte in the sample.

Abstract: The binding mode of the antiviral compounds have been characterized through a variety of biophysical and structural studies, elaborating on the proposed aggregation mechanism of action. We demonstrate the direct binding of these antiviral compounds to NP using thermal shift enhancement assay (TSE) and NMR. In addition, we have completed a detailed analysis of the oligomerization mechanism of action using dynamic light scattering, analytical ultracentrifugation, and surface plasmon resonance (SPR). Structure determination using x-ray crystallography confirmed the proposed compound-induced oligomerization mechanism of action. The co-crystal structure revealed that two compounds bound in an anti-parallel fashion bridging two NP monomers, inducing a novel non-native NP oligomer.

Abstract: Herein is reported a polypeptide-polynucleotide-complex as therapeutic agent and its use as tool for the targeted delivery of an effector moiety. The polynucleotide part of the complex is essentially resistant to proteolytic and enzymatic degradation in vivo. Additionally the polypeptide part specifically binds to a compound or structure such as a tissue or organ, a process or a disease. Thus, one aspect as reported herein is a polypeptide-polynucleotide-complex comprising a) a polypeptide specifically binding to a target and conjugated to a first member of a binding pair, b) a polynucleotide linker conjugated at its first terminus to the second member of the binding pair, and c) an effector moiety conjugated to a polynucleotide that is complementary to at least a part of the polynucleotide linker.

Abstract: The invention relates to compositions of vault complexes containing recombinant membrane lytic proteins, such as an adenovirus protein VI lytic domain, and methods of using the vault complexes to facilitate delivery and entry of a biomolecule into a cell or subject.

Abstract: The present invention provides a polynucleotide delivery system including a cationic polymer to which a rabies virus glycoprotein (RVG)peptide is bound, wherein the cationic polymer includes a biodegradable bond, and a method of delivering polynucleotides to a target cell by using the delivery system.

Abstract: Compositions and methods are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The protein prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties.

Abstract: The invention provides modified DNA-binding kinetochore polypeptides, wherein the modified DNA binding kinetochore polypeptides comprise a heterologous DNA binding domain. The invention further provides engineered kinetochores containing the modified kinetochore polypeptides. Further provided are artificial chromosomes containing an engineered kinetochore. Cells containing an artificial chromosome containing an engineered kinetochore are also provided. Methods for producing and methods of using the engineered kinetochore, artificial chromosome, and cells are also provided.

Abstract: Described herein are compositions and methods of use of targeted delivery complexes for delivery of siRNA to a disease-associated cell, tissue or pathogen. The targeted delivery complex comprises a targeting molecule, such as an antibody or fragment thereof, conjugated to one or more siRNA carriers. In preferred embodiments the siRNA carrier is a dendrimer or protamine and the targeting molecule is an anti-cancer antibody, such as hRS7. More preferably, the antibody or fragment is rapidly internalized into the target cell to facilitate uptake of the siRNA. Most preferably, the targeted delivery complex is made by the DNL technique. The compositions and methods are of use to treat a variety of disease states, such as cancer, autoimmune disease, immune dysfunction, cardiac disease, neurologic disease, inflammatory disease or infectious disease.

Abstract: Novel stable, concentrated, biologically active and ready-to-use lipid-comprising drug delivery complexes and methods for their production are described. The biological activity of the complexes produced are comparable to the formulations prepared according to the prior art admixture method and upon purification, the complexes produced by the method of this invention are 50 to 500 fold more concentrated than the complexes formed by admixture. The method described herein provides for the large scale production of lipid-comprising drug delivery systems useful for gene therapy and other applications.

Abstract: The present invention relates to an RNAi-inducing nucleic acid molecule having a new structure and the use thereof, and more particularly to a novel nucleic acid molecule having a structure comprising a first strand, which is 24-121 nt in length and comprises a region complementary to a target nucleic acid, and a second strand which is 13-21 nt in length and has a region that binds complementarily to the region of the first strand, which is complementary to the target nucleic acid, so that the nucleic acid molecule inhibits the expression of a target gene with increased efficiency, and to a method of inhibiting the expression of a target gene using the nucleic acid molecule. The nucleic acid molecule structure of the present invention increases the efficiency with which the nucleic acid molecule inhibits the target gene.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The present invention relates to the phosphohistidine analogs of the present invention which of the formula (I) and the hapten containing the residue of same. It also relates to the hapten conjugated to a carrier molecule and the isolated antibodies raised against the immunogens, said antibodies recognizing polypeptide containing a phosphorylated histidine or the phosphotriazole residue but it does not recognize an amino acid or polypeptide that is not phosphorylated or a polypeptide which is phosphorylated on amino acids other than histidine but not on histidine.

Abstract: The invention relates to a method for detecting the presence of a gynaecological growth, in particular for the diagnosis of endometriosis. The invention also relates to a method of identifying a biomarker for detecting the presence of a gynaecological growth and to biomarkers identified by said method.

Abstract: The present invention relates to compositions and methods for detection and quantification of individual target molecules in biomolecular samples. In particular, the invention relates to coded, labeled probes that are capable of binding to and identifying target molecules based on the probes' label codes. Methods of making and using such probes are also provided. The probes can be used in diagnostic, prognostic, quality control and screening applications.

Abstract: Compositions for inducing or enhancing immunogenicity of a tumor comprise bi- and multi-specific aptamers binding to a tumor cell and an immune cell. These compositions have broad applicability in the treatment of many diseases, including cancer.

Abstract: Universal flu vaccines are disclosed. The vaccines induce broad and sustained protection against a wide range of influenza A viruses, reduce the need for annual vaccination campaigns with vaccines based upon viral strains predicted to be the predominant circulating strains, and ameliorate the threat of future pandemics that can potentially kill millions.

Abstract: Molecular signatures that function as very sensitive diagnostic biomarker for myocarditis, heart disease and disorders thereof, are identified.

Abstract: The invention is based on the surprising finding that proteins regulated by excessive EGFR signalling in the liver may be used as biomarkers in the diagnosis, prognosis and/or monitoring of treatment of diseases, including liver cell dysplasia or hepatocellular carcinoma (HCC), wherein the protein is selected from a first group consisting of Arginase type II, 4931406C07Rik (Ester hydrolase C11orf54 homolog), Akr1c12 protein, Alanyl-tRNA synthetase, Aldo-keto reductase family 1 member C14, Aldo-keto reductase family 1 member C6, Aldolase 3, Alpha glucosidase 2, Beta 5-tubulin, Cai protein (Pdia4), cDNA sequence BC021917 (dihydroxyacetone kinase 2 homolog), Farnesyl diphosphate synthetase, Fatty acid binding protein 5 epidermal, Inosine triphosphatase, Interleukin 25, Kininogen 1, LIM and SH3 protein 1, Major vault protein, Nucb1 protein, Poly(rC) binding protein 2; heterogeneous nuclear ribonucleoprotein X, Psmd11 protein, RIKEN cDNA 2410004H02, Rps12 protein, Sars1 protein, Sorcin, T43799 proteasome protein p

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: The present invention includes compositions, methods and kits for directing an agent across the nuclear membrane of a cell. The present invention includes a Karyopherin beta2 translocation motif in a polypeptide having a slightly positively charged region or a slightly hydrophobic region and one or more R/K/H-X(2-5)-P-Y motifs. The polypeptide targets the agent into the cell nucleus.

Abstract: The invention in suitable embodiments is directed to an isolated protein comprising one or more amino acid sequences, each amino acid sequence capable of being functionalized and/or attached in whole and/or in part to one or more or a plurality of elements of one or more types including to cargo elements, forming a composition of elements suitable for use as an in vivo and/or in vitro medicament to treat one or more biological species.

Abstract: Provided herein are methods and compositions for controlling assembly of modified viral core proteins, for example, into a viral capsid or a nanocage. In some embodiments, the disclosed modified viral core proteins comprise at least one mutation or modification that can substantially prevent assembly of the viral core proteins until assembly is desired. In some embodiments, assembly of the viral core proteins may be triggered, for example, by contacting the viral core proteins with a reducing agent and/or by reducing the concentration of a denaturant. The viral core proteins may self-assemble to form a viral capsid or nanocage.

Abstract: The present invention provides an immunogenic composition comprising a T-cell antigen in association with a rhamnose monosaccharide and/or Forssman disaccharide, and corresponding methods for inducing immune response. The T-cell antigen may be for example, a tumor vaccine, such as a tumor cell or one or more tumor antigens. The invention takes advantage of the naturally high titers of anti-Rhamnose and/or anti-Forssman disaccharide in humans to target vaccine compositions to antigen presenting cells.

Abstract: Provided is a biomarker for detecting cancer, in particular prostate cancer in a male subject, the biomarker comprising at least one homeodomain containing transcription factor, such as a HOX peptide or EN-2 peptide, or a fragment thereof. The use of said biomarker in detecting and/or treating prostate cancer is provided, together with methods and kits therefor.

Abstract: A recombinant fluorescent protein nanoparticle having high fluorescence intensity and a method of detecting a target material using the same are provided. The protein nanoparticle has higher fluorescence intensity than a fluorescent protein, and is resistant to denaturation of the fluorescent protein at room temperature, thereby having higher structural stability than the fluorescent protein itself. In addition, since a self-assembled protein is used as a fusion partner of the fluorescent protein, the protein nanoparticle is biocompatible and safe. Moreover, when a linker peptide is additionally inserted into the protein nanoparticle, a suitable distance between the self-assembled protein and the fluorescent protein is maintained, thereby considerably increasing fluorescence intensity of the protein nanoparticle. The probe-binding protein nanoparticle can control distances between the fluorescent proteins on the surface thereof, thereby maximizing fluorescence intensity.

Abstract: The present invention generally relates to processes and methods of peptide and protein synthesis. The present invention also relates to specific compounds for use in such processes and methods. It is shown herein that peptides with a C-terminal tertiary N,N-bis(2-mercaptoethyl)-amide (BMEA) undergo N-to-S acyl transfer at weakly acidic pH to form a transient thioester which can be captured for direct ligation with a cysteinyl peptide. These C-terminal BMEA peptides are easily prepared with standard Fmoc solid-phase synthesis protocols, thus giving a very convenient access to the thioester components for native chemical ligation.

Abstract: This invention provides Sso7-polymerase conjugates that exhibit improved activity in a polymerase reaction.

Abstract: The method pertains to a peptide including the amino acid sequence SEQ ID NO: 1, or a peptide including an amino acid sequence having 93%, in particular 95%, particularly 98% sequence identity homology with the sequence SEQ ID NO: 1, in order to obtain a transporter intended for the internalization of a molecule of diagnostic or therapeutic interest into the target cells.

Abstract: Compositions including an antibody single-chain variable fragment (scFv) conjugate that specifically binds to ROR1 tumor-associated antigen are provided. The anti-ROR1 scFv antibody and conjugates may include a biologically-active molecule. Such conjugates may comprise a chimeric receptor to direct T cells to respond to ROR1 cancer cells, Methods to use the scFV conjugates to target cells expressing ROR1 for therapeutic and diagnostic purposes are also provided.

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: The invention provides compositions of influenza proteins, such as matrix and nucleoprotein, that are presented to an individual's immune system as multimeric displays to induce an immune response. The compositions are optionally associated with any type of immunomodulatory compound (IMC) comprising an immunostimulatory sequences (ISS). The invention further provides compositions of influenza matrix and nucleoproteins that can induce cellular and/or humoral immune response. The invention also provides methods of making and using these compositions, e.g., as a vaccine, for ameliorating symptoms associated with infection with influenza virus or for reducing the risk of infection with influenza virus.

Abstract: The present invention regards a method for providing a diagnosis for small cell lung carcinoma and for typical carcinoid tumor by using a panel of protein biomarkers which are differentially expressed and a method for screening compounds.

Abstract: Methods, compositions and kits are provided for treating a subject exposed to or at risk for exposure to a disease agent using a pharmaceutical composition including at least one recombinant heteromultimeric neutralizing binding protein including two or multiple binding regions, such that the binding regions are not identical, and each binding region specifically binds a non-overlapping portion of the disease agent, thereby treating the subject for exposure to the disease agent. In a related embodiment, the heteromultimeric neutralizing binding protein includes two or multiple binding regions that neutralize a plurality of disease agents. In certain embodiments, the disease agent includes a bacterium, a bacterial protein, a virus, a viral protein, a cancer cell, and a protein or molecule produced therefrom. In certain embodiments, the disease agent is a plurality of different disease agents.

Abstract: According to some embodiments, methods for covalently or non-covalently conjugating an antibody (e.g., hu3S193 or other humanized antibody) or functional fragment thereof with an siRNA molecule (e.g., anti-STAT3 siRNA) is provided. Such methods may include (1) modifying an antibody or functional fragment thereof with a linker to provide a linker-modified antibody, combining a target siRNA with a disulfide containing aldehyde linker to provide a linker-modified target siRNA and combining the linker-modified target siRNA with linker-modified antibody to form an antibody-siRNA complex; or (2) modifying an antibody or functional fragment thereof with a (Arginine)9 peptide to form an antibody-9R complex and associating an siRNA molecule with the antibody-9R complex to form an electrostatic antibody-9R:siRNA complex. In another embodiment, an antibody-siRNA conjugate may be used in methods for suppressing or silencing STAT3 protein expression in a cancer cell.

Abstract: The present invention relates to a new streptavidin muteins. This mutein is The muteins are capable of oligomerization to form tetramers, with relatively strong subunit interactions, dissociation constant (KD) for biotin in this mutein in the range of 10?7 to 10?8M, off-rate (koff) for the bound biotin in the streptavidin-biotin complex in the range of 10?4 sec?1, stable enough to allow reuse, and producible producable with reasonable production yield via secretion in a soluble functional state without the requirement of refolding streptavidin via the tedious and expensive denaturation and renaturation processes.

Abstract: The present disclosure relates to RNAi agents useful in methods of treating Beta-ENaC-related diseases such as cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and obesity-associated hypertension, using a therapeutically effective amount of a RNAi agent to Beta-ENaC.

Abstract: Methods, systems and kits are provided for detecting and quantifying multiple immunogens in a sample via consecutive addition of quantifiable extenders to immunogen bound complexes of immunogen binding agent attached to a DNA containing an RNA polymerase promoter.

Abstract: Nanoconstructs having three components: (1) biodegradable nanopolymers and nanoparticles, (2) immunodrugs such as CpG, and a (3) tumor binding device, which are actively targeted to tumor cells such as melanoma cells through receptor-mediated uptake and methods of using the same are described. Antitumor immunity is further enhanced by combination of PG-CpG nanoconstructs with agonists of positive costimulatory signals and inhibitors of negative immune regulatory signals.

Abstract: This invention relates to treatment of nerve injuries and regeneration of nerves and nerve function in the acutely and chronically lesioned central and peripheral nervous system. The invention provides a pharmaceutical composition comprising histone, e.g., H1. It was surprisingly shown that histones, in particular histone H1, can be used for the preparation of a pharmaceutical composition for treatment and/or prevention of acute and chronic injuries to the central and peripheral nervous system, for promoting growth and/or regrowth of nerves and enhancing formation of synapses and synaptic plasticity, and for neuroprotection.

Abstract: The disclosure relates to methods and composition for generating nanoscale devices, systems, and enzyme factories based upon a nucleic acid nanostructure the can be designed to have a predetermined structure.

Abstract: The present invention provides reagents and methods for the introduction of analogues of methyl or acetyl lysine into histone proteins.

Abstract: The present invention concerns compositions and use of multivalent and/or multispecific antibodies or immunoconjugates, preferably made by the dock-and-lock technique. The antibodies or immunoconjugates may comprise a first and second polypeptide, each comprising VH and VL domains in series, wherein the first and second polypeptides bind to each other, wherein a VH domain on one polypeptide binds to a complementary VL domain on the other polypeptide to form an antigen binding site, wherein VH and VL domains on the same polypeptide do not bind to each other and wherein one polypeptide is attached to the amino terminal end of a CH1 domain and the other polypeptide is attached to the amino terminal end of a CL domain. The carboxyl terminal end of the CH1 domain may be attached to a CH2-CH3 domain. The antibodies or immunoconjugates are of use to treat a wide variety of diseases.

Abstract: Four peptide nucleic acid probes (PNA) are for the detection of Helicobacter pylori and/or response analysis of Helicobacter pylori strains to clarithromycin. The probes are based in molecular biology methods, namely fluorescence in situ hybridization (FISH) that are used in H. pylori clarithromycin susceptibility diagnosis in several sample types, including clinical isolates and biopsies. Due to physical and chemical characteristics inherent in its structure, the probes allow a faster and more sensitive hybridization. A kit may use one or several probes described here and the related process of detection or quantification. The kit identifies H. pylori and its response to clarithromycin in clinical samples.

Abstract: The invention provides methods for enriching methyl-CpG sequences from a DNA sample. The method makes use of conversion of cytosine residues to uracil under conditions in which methyl-cytosine residues are preserved. Additional methods of the invention enable to preservation of the context of me-CpG dinucleotides. The invention also provides a recombinant, full length and substantially pure McrA protein (rMcrA) for binding and isolation of DNA fragments containing the sequence 5?-CMeCpGG-3?. Methods for making and using the rMcrA protein, and derivatives thereof are provided.

Abstract: The present invention provides novel nicotine hapten compounds and nicotine immunoconjugates which can be used for in vivo production of antibodies that specifically bind to nicotine. The invention also provides methods of using vaccines comprising the nicotine immunoconjugates in active or passive immunization protocols. The compositions and methods of the invention are useful for prevention and treatment of nicotine addiction.

Abstract: The present invention relates to a complex of a protein comprising zinc oxide-binding peptides and zinc oxide nanoparticles, to the use thereof as a drug delivery carrier for manufacturing medicines, and to a vaccine composition and a contrast agent comprising the composite. The protein comprising zinc oxide-binding peptides significantly improves the in vivo availability of zinc oxide-binding peptides, and therefore the complex of the present invention can be used not only as a drug delivery carrier for in vivo drug delivery or intracellular drug delivery, but also for in vivo imaging or cell imaging. The complex can be used for producing separating agents for effectively separating biological materials, therapeutic agents for hyperthermia, etc., contrast agents for MRI, and beads applicable to biosensors.

Abstract: The present disclosure provides an isolated protein comprising an antibody heavy chain variable region (VH) comprising a negatively charged amino acid at position 28 and/or 31 and/or 32 and/or 33 and/or 35 according to the numbering system of Kabat, the protein capable of binding specifically to an antigen.

Abstract: The present disclosure provides substantially monodisperse random coil polypeptides, vectors encoding the polypeptides, conjugates containing the polypeptides, methods for their preparation, and their uses in nucleic acid separations, DNA sequencing, and other applications requiring high monodispersity.

Abstract: The present invention provides a process called “Immune Banking” that enhances vaccine efficacy by exploiting existing humoral responses. The process involves tagging new antigens with molecular markers recognized by an existing anti-body response. This recognition of the tagged vaccine components enhances adaptive immune responses to the new vaccine.