Abstract: This disclosure provides peptides, polypeptides, fusion polypeptides, compositions, and methods for enhancing or increasing the stability of a polypeptide (e.g., Taq polymerase). Such peptides, polypeptides, fusion polypeptides, or compositions include polypeptides linked to a peptide tag that enhances the stability of the polypeptide. The peptides, polypeptides, fusion polypeptides, compositions may also enhance the activity, specificity, and/or fidelity of other polypeptides in a reaction mixture. The disclosure also provides methods of using such peptides, polypeptides, fusion polypeptides, compositions.

Abstract: Compositions, methods, and systems are provided for fluorescent polymerase enzyme substrates comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Fluorescent polymerase enzyme substrates of the invention have a protein shield between the fluorescent dye moieties and nucleotide moieties of the polymerase enzyme substrate. The polymerase enzyme substrates have a nucleotide component and a dye component, each attached to a protein. The attachments can be covalent. The protein can, for example, prevent the direct interaction of the fluorescent dye moiety with the enzyme when carrying out nucleotide synthesis, preventing photodamage to the enzyme. The polymerase enzyme substrates of the invention can have multiple dyes and multiple nucleotide moieties.

Abstract: Polypeptide products, methods, pharmaceutical compositions, and kits are provided for treating a subject exposed to, or at risk for exposure to, C. difficile microbial pathogens and toxin B produced by C. difficile (TcdB) pathogens. The methods, compositions and kits include a single domain, anti-TedB VHH polypeptide (antibody), or toxin B binding portion thereof, that specifically binds to and/or neutralizes TedB and treats or prevents illness and disease associated with C. difficile infection and TedB intoxication. The anti-TcdB VHHs, or toxin B binding portion thereof, may be recombinantly produced.

Abstract: Nucleotides encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein are provided herein. Also describe are mRNA constructs that can be used to express CFTR protein in vitro or in vivo. The mRNA constructs can be formulated in a lipid formulation and administered via inhalation to treat cystic fibrosis.

Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

Abstract: Implementations can identify a given assistant device from among a plurality of assistant devices in an ecosystem, obtain device-specific signal(s) that are generated by the given assistant device, process the device-specific signal(s) to generate candidate semantic label(s) for the given assistant device, select a given semantic label for the given semantic device from among the candidate semantic label(s), and assigning, in a device topology representation of the ecosystem, the given semantic label to the given assistant device. Implementations can optionally receive a spoken utterance that includes a query or command at the assistant device(s), determine a semantic property of the query or command matches the given semantic label to the given assistant device, and cause the given assistant device to satisfy the query or command.

Abstract: This disclosure relates mRNA therapy for the treatment of ornithine transcarbamylase deficiency (OTCD). mRNAs for use in the invention, when administered in vivo, encode human ornithine transcarbamylase (OTC), isoforms thereof, functional fragments thereof, and fusion proteins comprising OTC. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of OTC expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic ammonia associated with deficient OTC activity in subjects.

Abstract: This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins.

Abstract: Described herein are compositions and methods that are used to increase the expression of SCN2A, which may be used to treat neurological or psychiatric disorders. Antisense oligonucleotides that target upstream open reading frames (uORFs) may be administered to prevent translation initiation from a uORF to increase expression from a primary ORF (pORF), thus increasing the levels of SCN2A protein.

Abstract: The present invention is directed to an aptamer composition comprising at least one oligonucleotide consisting of: deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, and mixtures thereof; wherein said aptamer composition has a binding affinity for one or more bacterial species from the genera Prevotella and Porphyromonas.

Abstract: A DNA complex includes a carrier and DNA immobilized on the carrier. 80% or more by mass of the DNA is single-stranded DNA, the DNA has an average molecular weight of 500,000 or less, and the DNA content is more than 15% by mass and 50% or less by mass of the DNA complex. The carrier contains an inorganic material. The DNA complex has an average particle size of 10 ?m or more.

Abstract: Methods, kits and compositions, in some embodiments, may include a thermostable DNA guided Argonaute protein for example TtAgo, a thermostable single-stranded DNA binding protein (SSB) for example, ET SSB, and, optionally, a strand-displacing polymerase. A SSB may allow (a) Argonaute/guide DNA complexes to substantially enhance cleavage efficiency of single- and double-stranded DNA substrates; (b) the use of longer guide DNAs (e.g., guide DNAs that are at least 24 nucleotides in length) and/or (c) increases in the sequence specificity of Argonaute-mediated binding and cleavage reactions.

Abstract: The present invention provides a method for prominently inhibiting the production in fungi of mycotoxin, which has serious effects on health of humans and other animals, and provides a mycotoxin production inhibitor. Mycotoxin content such as deoxinivalenol (DON) in harvested crops can be reduced without a correlation with the control effects against fungi by spraying a fungicide containing a benzimidazole-type fungicidal compound such as thiophanate-methyl as an active ingredient onto food crops such as wheat, barley, and the like. Concomitant use of the benzimidazole-type fungicidal compound and a sterol biosynthesis inhibitor (SBI agent) such as tebuconazole can further enhance the effect.

Abstract: Chromatin-associated proteins and other factors and their related methods and compositions are isolated and identified.

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: The present invention provides an isolated methyl degron peptide and a fusion protein comprising a methyl degron peptide. Also, the present invention provides screening methods for agents affecting protein lifespan and anti-cancer agents. Moreover, the present invention provides methods of controlling protein lifespan, regulating protein expression, and treating cancers by using a methyl degron peptide or a methyl degron gene.

Abstract: The present invention discloses a transcription activator-like effector-based strategy, termed “TALEColor”, for labeling specific repetitive DNA sequences in human chromosomes. TALEs were custom designed for human telomeric repeats and fused with any of numerous fluorescent proteins (FPs). TALE-telomere-FP fusion proteins were used to detect telomeric sequence in both living cells and fixed cells. Using human cells with different average telomere lengths, TALEColor signals correlated positively with telomere length. TALEs were also designed to detect centromeric sequences unique to specific chromosomes, enabling localization of these specific human chromosomes in live cells. These methods may have significant potential both for basic chromosome and genome research as well as in clinical applications.

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 sequence and structural features of single-stranded (ss)RNA molecules required to mediate target-specific nucleic acid modifications by RNA-interference (RNAi), such as target mRNA degradation and/or DNA methylation.

Abstract: It is an object of the present invention to provide: a polyion complex that sufficiently retains a photosensitizing substance in serum and is excellent in terms of structural stability; a nucleic acid polyplex as a constituent thereof; and a device and a kit for delivering a nucleic acid into a cell. The nucleic acid polyplex of the present invention comprises a cationic polymer represented by general formula (1) and a nucleic acid. The polyion complex of the present invention comprises the nucleic acid polyplex of the present invention and an anionic photosensitizing substance.

Abstract: The invention relates to a nucleic acid which is stabilised against decomposition by exonucleases. Said nucleic acid contains the following constituents: a) a code sequence coding for a defined protein, b) optionally, a promoter sequence controlling the expression of the code sequence, and c) at least one molecule A added to an end of the linear sequence containing the constituents a and b, said molecule being linked to a non-immobilised, volumic molecule B.

Abstract: The present invention concerns a pharmaceutical composition comprising virtosomes isolated from non-dividing cells or the medium in which the cells are grown, for use in the inhibition of tumour growth and/or prevention of metastases.

Abstract: The invention relates to mutant forms of lysenin. The invention also relates to analyte characterisation using lysenin.

Abstract: Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.

Abstract: A method for lattice design via multivalent linkers (LDML) is disclosed that introduces a rationally designed symmetry of connections between particles in order to achieve control over the morphology of their assembly. The method affords the inclusion of different programmable interactions within one linker that allow an assembly of different types of particles. The designed symmetry of connections is preferably provided utilizing DNA encoding. The linkers may include fabricated “patchy” particles, DNA scaffold constructs and Y-shaped DNA linkers, anisotropic particles, which are preferably functionalized with DNA, multimeric protein-DNA complexes, and particles with finite numbers of DNA linkers.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: Methods for screening libraries of polypeptides for biologically activity on cells. For example, polypeptides can be synthesized and encapsulated along with their coding sequences in microcapsules of an emulsion. Emulsion microcapsules can then be fused with microcapsules comprising test cells and biological activity on the cells is assessed to identify biologically active polypeptides and nucleic acid molecules encoding the same.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidised polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: The present invention features compositions and methods that make use of complexes comprising one or more inhibitory nucleic acids and a targeting polypeptide, wherein the targeting polypeptide consists of a cell surface receptor ligand. The compositions can be used in methods of silencing gene expression in a cell, in delivering agents to a target cell, and in treating or preventing a disease or disorder in a subject.

Abstract: This disclosure provides universal influenza vaccines which can provide extended protection for several years, provide improved protection to circulating influenza strains that were not predicted accurately for annual vaccine manufacturing, and provide protection against newly emerging strains of influenza virus which carry the potential for establishing global pandemics.

Abstract: Methods and constructs for RNA-guided targeting of transcriptional activators to specific genomic loci.

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 invention provides isolated fully human monoclonal anti-HRV antibodies, as well as method of making and using these antibodies. Anti-HRV antibodies of the invention prevent or treat subjects having HRV-infections, and related diseases, including, but not limited to, the common cold, nasopharyngitis, croup, pneumonia, bronchiolitis, asthma, chronic obstructive pulmonary disease (COPD), sinusitis, bacterial superinfection, and cystic fibrosis.

Abstract: The application describes a biosensor system to measure the presence of single molecules of interest or multiple molecules simultaneously in aqueous solutions without the need for trained personnel or dedicated laboratory space. The system uses a lab-on-a-chip platform to contain and manipulate a biosensor component that, through a series of controlled steps, converts the presence of each of the molecule/s of interest into a unique nucleic acid identifier designated by a specific sequence. The generation of the unique nucleic acid identifier is strictly correlated with the presence of the molecule of interest. The platform contains: multiple, sequential, interconnected chambers; transformer coils that induce magnetic fields; the potential for various electric fields; thermal controls; electronics for measurements; and power control.

Abstract: Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

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 bio-programmable crystallization of multi-component functional nanoparticle systems is Ascribed, as well as methods for such bio-programmable crystallization, and the products resultant from such methods. Specifically, the systems disclosed and taught herein are directed to improved strategies for the DNA-mediated self-assembly of multi-component functionalized nanoparticles into three-dimensional order surperlattices, wherein the functionalization of the nanoparticles with DNA is independent of either the composition of the material, or the shape of the nanoparticles.

Abstract: The present invention relates to a method of diagnosis, prognostic or treatment of neurodegenerative diseases, in particular Alzheimer's disease.

Abstract: A protein-immobilizing solid phase is a protein-immobilizing solid phase comprising an mRNA-nucleic acid linker-protein complex, obtained by linking the mRNA and the protein encoded by that mRNA through the nucleic acid linker, immobilized on the solid phase, wherein the nucleic acid linker has a photocleavage site and a solid phase binding site.

Abstract: The invention provides eukaryotic unicellular algae engineered to express a nucleosome alteration protein fused to a protein with affinity to the DNA binding site acting in coordination. An example is a LexA-p300 fusion protein, where the p300 is derived from Chlamydomonas. The LexA binding domain guides the p300 to the binding site and the p300 loosens the nucleosome structure by acetylating histones within proximity of the transgene, thus remodeling the local chromatin structure to allow for high-level expression.

Abstract: The present invention concerns chimeric or humanized antibodies or antigen-binding fragments thereof that comprise specific CDR sequences, disclosed herein. Preferably, the antibodies or fragments comprise specific heavy and light chain variable region sequences disclosed herein. More preferably, the antibodies or fragments also comprise specific constant region sequences, such as those associated with the nG1m1,2 or Km3 allotypes. The antibodies or fragments may bind to a human histone protein, such as H2B, H3 or H4. The antibodies or fragments are of use to treat a variety of diseases that may be associated with histones, such as autoimmune disease (e.g.

Abstract: A nucleic acid linker is for producing a complex of mRNA and a protein encoded by that mRNA, comprising one 3?-terminal region and two branched 5?-terminal regions, wherein the 3?-terminal region comprises a single-stranded polynucleotide segment able to hybridize with the sequence on the 3?-terminal side of the mRNA, and an arm segment that branches off from the single-stranded polynucleotide segment and has a linking segment with the protein on the terminal thereof, and one of the two 5?-terminal regions has a binding site with the 3?-terminal of the mRNA.

Abstract: The present invention provides methods of achieving directed evolution of viruses by in vivo screening or “panning” to identify viruses comprising scrambled AAV capsids having characteristics of interest, e.g., tropism profile and/or neutralization profile (e.g., ability to evade neutralizing antibodies). The invention also provides scrambled AAV capsids and virus particles comprising the same.

Abstract: The current invention relates to a method for identifying a subject at risk of developing an idiopathic inflammatory myopathy and/or diagnosing a subject suffering from an idiopathic inflammatory myopathy, preferably wherein said idiopathic inflammatory myopathy is Inclusion Body Myositis. The invention provides methods in diagnosis, use of specific antigens, and kits for use in studying the presence or absence of (auto)antibodies in samples derived from subjects.

Abstract: Using a nucleic acid construct, association of a polypeptide with a sequence coding therefor and screening of a polypeptide that binds to a target substance are carried out, which nucleic acid construct comprises a 5?-untranslated region and a coding region, wherein the above-mentioned coding region comprises a sequence coding for a polypeptide subjected to be displayed, a sequence coding for a first nucleic acid binding polypeptide, and a sequence coding for a second nucleic acid binding polypeptide; the above-mentioned 5?-untranslated region comprises a first sequence capable of binding to a first nucleic acid binding polypeptide and a second sequence capable of binding to second nucleic acid binding polypeptide; and, when the above-mentioned nucleic acid construct is introduced in a translation system, a fusion protein translated from the coding region of the above-mentioned nucleic acid construct forms a complex with an RNA corresponding to the above-mentioned nucleic acid construct.

Abstract: The invention relates to a method for detecting and measuring the presence of mono-nucleosomes and oligo-nucleosomes and nucleosomes that contain particular histone variants and the use of such measurements for the detection and diagnosis of disease. The invention also relates to a method of identifying histone variant biomarkers for the detection and diagnosis of disease and to biomarkers identified by said method.

Abstract: The invention provides methods for isolating cell-type specific mRNAs by selectively isolating ribosomes or proteins that bind mRNA in a cell type specific manner, and, thereby, the mRNA hound to the ribosomes or proteins that bind mRNA. Ribosomes, which are riboprotein complexes, bind mRNA that is being actively translated in cells. According to the methods of the invention, cells are engineered to express a molecularly tagged ribosomal protein or protein that binds mRNA by introducing into the cell a nucleic acid comprising a nucleotide sequence encoding a ribosomal protein or protein that binds mRNA fused to a nucleotide sequence encoding a peptide tag. The tagged ribosome or mRNA binding protein can then be isolated, along with the mRNA bound to the tagged ribosome or mRNA binding protein, and the mRNA isolated and further used for gene expression analysis.

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: The invention relates to a nucleic acid which is stabilised against decomposition by exonucleases. Said nucleic acid contains the following constituents: a) a code sequence coding for a defined protein, b) optionally, a promoter sequence controlling the expression of the code sequence, and c) at least one molecule A added to an end of the linear sequence containing the constituents a and b, said molecule being linked to a non-immobilised, volumic molecule B.

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.