Abstract: Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of chronic and acute conditions. Such conditions may be caused by disease, be symptoms or sequelae of disease. Chronic and acute conditions may be due to viral infections such as HIV and AIDS, neoplastic diseases stroke, kidney disease, urinary incontinence, autoimmune disorders, Parkinson's disease, prostate hypertrophy, aging, or the treatment of such diseases. Additional compositions and methods are provided which employ a phorbol ester or derivative compound in combination with at least one additional agent to yield more effective treatment tools against acute and chronic conditions in mammalian subjects.

Abstract: Method of in vitro measurement of the presence of factors that are able to neutralize asparaginase activity in a sample of blood, plasma, serum or derived medium that may contain asparaginase neutralizing factors, obtained from a patient, comprising mixing of said sample with asparaginase, incubation of said mixture, then measurement of the residual asparaginase activity in the mixture and determination or quantification of the presence of said neutralizing factors. Method for predicting the efficacy of a treatment with asparaginase.

Abstract: Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

Abstract: The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects. Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

Abstract: The present invention relates to methods of promoting the survival of cells by treating the cells with acid ceramidase. A kit for promoting ex vivo cell survival is also disclosed, as is a method of predicting in vitro fertilization outcome of a female subject.

Abstract: Some aspects of this disclosure provide strategies, methods, and reagents for selecting a site-specific endonuclease based on determining its target site preferences and specificity. Methods and reagents for determining target site preference and specificity are also provided.

Abstract: Some aspects of this disclosure provide strategies, methods, and reagents for determining nuclease target site preferences and specificity of site-specific endonucleases. Some methods provided herein utilize a novel “one-cut” strategy for screening a library of concatemers comprising repeat units of candidate nuclease target sites and constant insert regions to identify library members that can been cut by a nuclease of interest via sequencing of an intact target site adjacent and identical to a cut target site.

Abstract: Compositions and methods for inhibiting cancer cell metastasis and inflammation are disclosed. The methods generally involve administering to a subject a composition containing an agent that selectively inhibits the binding of p68 RNA helicase to calmodulin (CaM) in the cells.

Abstract: The present invention provides polypeptides that bind to immunoglobulin G and methods for their use.

Abstract: The present invention is related to a compound that includes a lysosomal enzyme and a targeting moiety, for example, where compound is a fusion protein including iduronate-2-sulfatase and Angiopep-2. In certain embodiments, these compounds, owning to the presence of the targeting moiety can crossing the blood-brain barrier or accumulate in the lysosome more effectively than the enzyme alone. The invention also features methods for treating lysosomal storage disorders (e.g., mucopolysaccharidosis Type II) using such compounds.

Abstract: The present invention provides compositions and methods for effective treatment of a lysosomal acid lipase deficiency (LALD) disease, in particular, Wolman's disease and Cholesteryl Ester Storage Disease (CESD). Among other things, the present invention provides a method of treating developmental impairment or malnutrition in an individual suffering from a lysosomal acid lipase deficiency (LALD) disease, comprising administering to the individual a therapeutic effective amount of a lysosomal acid lipase.

Abstract: Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (?)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (?)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system.

Abstract: The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

Abstract: The invention provides for the use of a therapeutic derived from a truncated lipoprotein lipase protein (LPL S447X), including nucleic acids encoding such proteins, for the treatment of conditions including LPL responsive conditions, such as cardiovascular disease, hypertension, LPL deficiency, high triglyceride levels, low HDL-cholesterol levels or atherosclerosis.

Abstract: The invention provides methods, compositions and kits for segregating a target nucleic acid from a mixed nucleic acid sample. The methods, compositions and kits comprise a non-processive endonuclease (e.g., a restriction enzyme) or an antibody that binds the target nucleic acid (e.g., has methylation specificity). The mixed nucleic acid sample can comprise prokaryotic and eukaryotic nucleic acid and/or nucleic acid from more than one prokaryotic or eukaryotic organisms.

Abstract: This invention provides compositions of active highly phosphorylated human N-acetylgalactosamine-6-sulfatase (GALNS), and pharmaceutical compositions and formulations thereof, methods of producing and purifying GALNS, and its use in the diagnosis, prophylaxis, or treatment of diseases and conditions, including particularly lysosomal storage diseases that are caused by, or associated with, a deficiency in the GALNS enzyme, e.g., Mucopolysaccharidosis IVa (MPS IVa or Morquio A syndrome).

Abstract: Methods for treatment and diagnosis of pervasive developmental disorders in humans are described.

Abstract: Purified Ref polypeptides with increased nuclease site-specific targeting activity, recombinant nucleic acids and cells for expression of such Ref polypeptides, and methods for using the Ref polypeptides in combination with RecA protein and variants thereof to effect targeted nuclease cleavage of a DNA duplex are disclosed.

Abstract: The invention includes a method of preventing or treating metastasis in a subject diagnosed with cancer, the method comprising determining whether at least one gene encoding one or more proteins is upregulated in a cancer tissue sample from the subject as compared to the level of expression of the at least one gene in a non-cancer control sample of the same tissue, and, if the at least one gene is upregulated in the cancer tissue sample from the subject, administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising one or more protein depleting agents.

Abstract: DNase I formulations for pulmonary administration and, more particularly, but not exclusively, a dry powder formulation comprising, as an active ingredient, human DNase I, methods, dry powder inhalation devices and systems for the therapeutic use thereof are provided.

Abstract: In certain embodiments compositions are provided that comprise a pentapeptide comprising the formula: C1-X2-X3-X4-C5 where C1 and C5 are independently selected cysteines or cysteine analogues, or other amino acids with sidechains suitable for cyclization, where the cysteines or cysteine analogs are attached to each other by a linkage that does not comprise X2, X3, and X4; where X2, X3, and X4 are independently selected amino acids; and the peptide, when administered to a cell alters APP signaling and/or switches APP processing from aberrant to normal. The compositions mitigate amyloid plaque formation.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: This invention relates generally to a therapeutic use of alkaline phosphatase to reduce or inhibit toxic effects associated with a bacterial infection in a subject.

Abstract: The invention is directed to treatment of systemic DNA mutation diseases accompanied with development of somatic mosaicism and elevation of blood extracellular DNA. The inventive method comprises introducing a DNASE enzyme into the systemic blood circulation of a patient in doses and regimens which are sufficient to decrease average molecular weight of circulating extracellular blood DNA in the blood of said patient.

Abstract: An inhalable pharmaceutical composition for pulmonary administration comprising human DNase I and a liquid carrier and, more particularly, but not exclusively, to methods, liquid pharmaceutical inhalation devices and systems for the therapeutic use thereof are provided.

Abstract: Plant-expressed human recombinant DNase proteins, nucleic acid constructs for expression of the human recombinant DNase I in plant cells, cells expressing the nucleic acid construct and therapeutic uses thereof are disclosed. Particularly, compositions and methods for treating pulmonary and/or respiratory conditions by inhalation of the plant-expressed human recombinant DNase I are provided.

Abstract: Provided herein is a composition and a method for treating nucleic acid-related eye disease.

Abstract: The present invention describes an unbiased catalytic tagging system to search for target substrates. Identification of substrates for specific baits is accomplished by utilizing an orthogonal system consisting of an E1 activating enzyme, an E2 ubiquitin-like conjugating enzyme, and baits that are fused to the E2 ubiquitin-like conjugating enzyme. The present invention thus reveals important mutually antagonistic substrates of specific baits.

Abstract: Disclosed herein are ?-galactosylceramide (?-GalCer) analogs and compositions thereof, methods of activating invariant Natural Killer T (iNKT) cells using said analogs, methods of treating diseases by activating iNKT cells using said analogs, and combination therapy of said analogs.

Abstract: Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

Abstract: A system for targeted delivery of agents (e.g., molecular probes, diagnostic agents, therapeutic agents, imaging agents, research or analytical compounds, enzymes, peptides, proteins, lipids, lipoproteins, sugars, hormones, vitamins, nucleic acids, viruses, bacteria, and/or cells) including use of a composition containing the agent and a targeting moiety, specific for a determinant at the target location. An exemplary composition of the system includes a targeting moiety of one of peptides ?3, 2?3, 3?3, A1, B7, B8, B9, B1O, and D6, specific for targeting ICAM-I. The system enables effective, versatile, and safe targeting and transport of agents. The system is useful in research applications, as well as in the context of translational science and clinical interventions.

Abstract: The present invention relates to a therapeutic comprising an osteopontin isoform a (“OPNa”) inhibitor where the OPNa inhibitor blocks activity of extracellular OPNa exon 4. The OPNa inhibitor is selected from the group consisting of (i) an exon-4 specific antibody or binding portion thereof; (ii) a peptide mimic of OPNa exon 4 or a fragment thereof; (iii) a nucleic acid aptamer that specifically binds to OPNa exon 4 or a fragment thereof; and (iv) a peptide inhibitor that binds to OPNa exon 4 or a fragment thereof. The present invention also relates to methods of inhibiting tumor growth and/or metastasis in a subject, treating a subject with chemotherapeutic resistance, and methods of increasing tumor cell sensitivity to a cancer therapeutic by administering an OPNa inhibitor according to the present invention.

Abstract: The present invention concerns a method for modulating the enzymatic activity of an enzyme, wherein said enzyme interacts with BMP, said method comprising the step of administering or inducing Hsp70, or a functional fragment or variant thereof, in a form suitable for allowing interaction between BMP and Hsp70, or said functional fragment or variant thereof, and thereby modulating the enzymatic activity of an enzyme interacting with BMP.

Abstract: The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.

Abstract: There are provided a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals. The lyophilized preparation of botulinum toxin according to the present invention can maintain an activity of botulinum toxin, and also exhibit excellent long-term storage stability even under conditions of high temperature, which may occur when botulinum toxin is stored, delivered, and processed.

Abstract: The present invention relates to a treatment by pulmonary delivery of a bioscavenger to animals as an effective antidote to prevent toxicity produced by exposure of an animal to nerve agents and other toxic substances.

Abstract: The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease). In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.

Abstract: The invention relates to a method of treating mucopolysaccharidoses using enzyme replacement therapy with chemically modified lysosomal enzymes. More specifically the method relates to administering chemically modified lysosomal enzymes intraperitoneal injection. In addition, the invention relates to treating type VII mucopolysaccharidoses or mucopolysaccharidoses type VII related bone lesions with a chemical modified ?-glucuronidase, wherein the modified ?-glucuronidase may be administered 5 weeks after birth, and or may be administered intraperitoneally.

Abstract: Methods for reducing the environmental impact of animal waste are described. In particular embodiments, the methods comprise administering to an animal an enzyme, such as alkaline phosphatase, that is effective to reduce the amount of a detrimental compound, such as ammonia or phosphorous, that is present in or released from animal waste. Also provided is a method for increasing phosphorus digestion in an animal. Compositions suitable for use in such methods are also described.

Abstract: Disclosed in certain embodiments is a method of inhibiting cell function comprising inducing the expression of a mRNA interferase that cleaves mRNA at GCU.

Abstract: Targeted antimicrobials are described and related, compositions, methods and systems.

Abstract: Acetyl xylan esterases and variants thereof having perhydrolytic activity are provided for producing peroxycarboxylic acids from carboxylic acid esters and a source of peroxygen. Multi-component peracid generation systems comprising an enzyme catalyst having perhydrolytic activity are also provided, as are methods of using the present enzyme catalyst to produce peroxycarboxylic acids. The polypeptide having perhydrolytic activity may be used to produce peroxycarboxylic acids suitable for use in a variety of applications such as cleaning, disinfecting, sanitizing, bleaching, wood pulp processing, paper pulp processing, and personal care applications.

Abstract: The present invention provides a site-directed mutated arginase and the preparation method thereof, and the use of said site-directed mutated arginase in preparing a medicament for treating an arginase-related disease. The present invention also provides a pegylated arginase and the preparation method thereof, and the use of said pegylated arginase in preparing a medicament for treating an arginase-related disease.

Abstract: The application relates to antimicrobial agents against Gram-negative bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-negative bacteria and a peptide stretch fused to the enzyme at the N- or C-terminus, as well as pharmaceutical compositions thereof. Moreover, it relates to nucleic acid molecules encoding such a fusion protein, vectors carrying the nucleic acid molecules and host cells transformed with either the nucleic acid molecules or the vectors. In addition, it relates to such a fusion protein for use as a medicament, in particular for the treatment or prevention of Gram-negative bacterial infections, as diagnostic means or as cosmetic substance. The application also relates to the treatment or prevention of Gram-negative bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff, of medical devices, of surfaces in hospitals and surgeries.

Abstract: A composition useful for the treatment of degenerative brain disease. A pharmaceutical composition comprising an effective amount of apamin as an active ingredient and an effective amount of at least another compound including a permeability enhancer and/or carrier molecule.

Abstract: Various embodiments of the invention provide human kinases and phosphatases (KPP) polypeptides and polynucleotides which identify and encode KPP. Embodiments of the invention also provide expression vectors, host cells, antibodies, agonists, and antagonists. Other embodiments provide methods for diagnosing, treating, or preventing disorders associated with aberrant expression of KPP.

Abstract: The present invention includes nanotubes or rods, methods and arrays using plasmonic-magnetic bifunctional nanotubes or rods comprising: one or more silica nanotubes or rods; one or more nanomagnets embedded in a portion of the silica nanotubes or rods; and plasmonic metal nanoparticles uniformly coating in or on at least a portion of the surface of the nanomagnets and the silica nanotubes surface-coated.

Abstract: Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of histone deacetylase 8 (HDAC8). Also described herein are methods of using such HDAC8 inhibitors, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of HDAC8 activity.

Abstract: Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.