Abstract: A conjugate comprises: (a) a mitochondrial membrane-permeant peptide; (b) an active agent or compound of interest such as a detectable group or mitochondrial protein or peptide; and (c) a mitochondrial targeting sequence linking said mitochondrial membrane-permeant peptide and said active mitochondrial protein or peptide. The targeting sequence is one which is cleaved within the mitochondrial matrix, and not cleaved within the cellular cytoplasm, of a target cell into which said compound is delivered. Methods of use of such compounds are also described.

Abstract: Disclosed is an invention for focally modulating the activity of a calcium channel in a mammal. In one aspect, the invention features a method that includes contacting a pre-determined tissue or organ region with a nucleic acid sequence encoding a GEM protein or a variant thereof to express the GEM protein or variant within the region. Typical methods further include expressing the GEM protein or variant so as to modulate the activity of the calcium channel. The invention has a wide spectrum of useful applications including treating a medical condition associated with unsuitable calcium channel activity.

Abstract: The present invention relates to nucleic acids and polypeptides encoded thereby, whose expression is modulated in brain microvascular endothelial cells undergoing early dynamic inflammation-induced changes in blood-brain barrier functionality. Such polypeptides are referred to as lipopolysaccharide-sensitive (LPSS) polypeptides herein. These nucleic acids and polypeptides may be useful in methods for controlling blood-brain barrier properties in mammals in need of such biological effects. This includes the diagnosis and treatment of disturbances in the blood-brain/retina barrier, brain (including the eye) disorders, as well as peripheral vascular disorders. Additionally, the invention relates to the use of anti-LPSS polypeptide antibodies or ligands as diagnostic probes, as blood-brain barrier targeting agents or as therapeutic agents as well as the use of ligands or modulators of expression, activation or bioactivity of LPSS polypeptides as diagnostic probes, therapeutic agents or drug delivery enhancers.

Abstract: The present invention relates to delivery, including transdermal delivery, of a therapeutically effective amount of a compound useful for modulating gap junction formation and function, including an oligonucleotide for reducing gap junction formation and function, and methods and compositions for treating a subject suffering from pain associated with a disease, disorder or condition and associated with pain, including but not limited to muscle pain, ligament pain, tendon pain, joint pain and post-operative pain.

Abstract: The innovative treatment strategy described here utilizes configurable microscopic medical payload delivery devices to act as a transport vector to deliver nuclear signaling proteins to specific cell types in the body. Utilizing probes on the exterior of the transport device, transport device locate specific target cell types in the body. Once a specific target cell type has been encountered, the configurable microscopic medical payload delivery device inserts its payload of nuclear signaling proteins into the target cell type. By delivering nuclear signaling proteins to specific cell types, genes can be activated or inactivated in those specific cell types. These medically therapeutic nuclear signaling proteins are intended to improve cell function or the longevity of the cell or eliminate cells that pose a hazard to the general health of the body.

Abstract: Provided are methods and compositions for enhancing the transmucosal absorption of bioactive peptides and proteins. More particularly, the invention provides compositions for enhancing the transmucosal absorption of bioactive peptides and proteins, such as exendin-4, PYY, PYY3-36, and GLP-1 and their analogs and derivatives, wherein the compositions comprise an absorption enhancing mixture of a cationic polyamino acid and a buffer that is compatible with the polyamino acid. Also provided are methods for enhancing the transmucosal absorption and bioavailability of bioactive peptides and proteins using such compositions.

Abstract: A novel class of transporter protein, referred to as SWEET, GLUE or Glü, is disclosed. These transporters provide a novel system for the transportation of sugars across membranes within a cell and between the inside and outside of a cell. Such transporters are useful for understanding and altering the sugar concentration within certain organs of an organism, and within certain organelles within the cell. These transporters are also useful in protecting plants from a pathogen attack.

Abstract: Described is a pharmaceutical composition comprising a compound(s) interfering with the biological activity of L1 and/or ADAM10 or their expression. Also described is the use of said compound(s) for the prevention/treatment of carcinomas like ovarian and endometrial carcinoma. Finally, the diagnosis of highly malignant forms of carcinomas which is based on the determination of the activity/expression of L1 and/or ADAM10 is described.

Abstract: The invention relates to a composition comprising a pharmaceutically active agent and a bioadhesive delivery system that provides for the oral delivery of a vaccine to animals, particularly aquatic animals.

Abstract: Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies, which immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

Abstract: The invention relates generally to methods of influencing central nervous system cells to produce progeny useful in the treatment of CNS disorders. More specifically, the invention includes methods of exposing a patient suffering from such a disorder to a reagent that modulates the proliferation, migration, differentiation and survival of central nervous system cells. These methods are useful for reducing at least one symptom of the disorder.

Abstract: The present invention relates to methods for augmenting SERCA2 mediated calcium ion transport into the sarcoplasmic reticulum of cardiac myocytes of a host. The method includes administering to host cardiac myocytes a zinc finger protein that induces expression of SERCA2a (or administering a nucleic acid molecule encoding such a protein), wherein expression of SERCA2a produces an augmentation in SERCA2 mediated calcium ion transport in treated myocytes, as compared to untreated myocytes. Also provided are methods of treating heart failure by administering to a patient in need thereof, a zinc finger protein or zinc finger protein fused to an effector domain, that induces expression of SERCA2a.

Abstract: The present invention relates generally to a method for modulating cell survival. Modulation of cell survival includes inducing, enhancing or otherwise promoting cell survival such as the survival of neural cells as well as facilitating cell death such as the death of targeted cancer cells. The modulation of cell survival is mediated by a region identified on the p75 neurotrophin receptor (p75NTR) required for death signalling. The present invention further provides genetic molecules which encode the death signalling region of p75NTR which are useful in antagonising death signal function as well as promoting cell death when expressed in targeted cells. The present invention also contemplates recombinant peptides, polypeptides and proteins as well as chemical equivalents, derivatives and homologues thereof which comprise the death signalling portion of p75NTR. Particularly useful molecules of the present invention comprise peptides corresponding to soluble forms of the death signalling portion of p75NTR.

Abstract: A mucosal absorption-enhancing agent is provided that enables oral, nasal or pulmonary administration of peptide drugs whose administration route has heretofore been limited to the injections due to their poor absorption from the mucosa. Specifically, the mucosal absorption of peptide drugs via intestinal, pulmonary or nasal route can be enhanced by allowing the peptide drugs with the C-terminal fragment (C-CPE) of an enterotoxin (CPE) produced by the bacterium Clostridium perfringens of the genus Clostridium, in particular with the C-CPE or its mutants resulting from the substitution and/or deletion of one or several amino acid residues of the C-CPE to act thereon. The composition for mucosal administration of the present invention significantly enhances absorption of peptide drugs, such as human parathyroid hormone hPTH(1-34), human ghrelin and human motilin, through the mucosa of small intestine, lung, nasal cavity and other mucosa.

Abstract: The present invention relates to methods of inhibiting capillary endothelial (CE) cell migration, the formation of CE networks and angiogenesis, and uses thereof for the purpose of treating angiogenesis-related diseases and disorders, particularly when the diseases or disorders are directly related aberrant angiogenesis Inhibition is achieved by inhibiting TRPV4 activity, such as the levels of TRPV4 expression, calcium influx through TRPV4, and/or the intracellular signaling from TRPV4 via ?1 integrin activation.

Abstract: The present invention provides new methods of treating wet type of age related macular degeneration by administering adiponectin (APN) or a functional fragment derived therefrom. One of the pathological complications of age related macular degeneration (AMD) is choroidal angiogenesis or choroidal neovascularization (CNV). The inventors discovered that the level of APN expression is significantly lower in the choroids of the laser-induced mouse model of choroidal angiogenesis or choroidal neovascularization (CNV) than that of the control mice and that administration of recombinant adiponectin (rAPN) or a peptide derived from the globular domain of the intact APN protein to the mouse model of CNV reduced the size of CNV significantly. These studies are the first to demonstrate the inhibitory effect of adiponectin on choroidal angiogenesis and thus provide the basis for treating a condition or disease involving angiogenesis, particularly age related macular degeneration, with administration of adiponectin.

Abstract: Peptides able to inhibit or activate the translocation or function of ?PKC are identified. Administration of the peptides for protection or enhancement of cell damage due to ischemia is described. Therapeutic methods to reduce damage to cells or to enhance damage to cells due to ischemia are also described, as well as methods for screening test compounds for ?PKC-selective agonists and antagonists.

Abstract: The present invention relates to novel muteins derived from human tear lipocalin having affinity to human c-Met receptor tyrosin kinase (c-Met). The invention also refers to a corresponding nucleic acid molecule encoding such a mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Abstract: The present invention provides for diagnosis or treatment of neurological or neuropsychiatric disorders involving abnormal dopamine neurotransmission. Methods and agents are provided for modulating dopamine transporter activity and modulating dopaminergic neurotransmission. Agents of the present invention include fragments of D2 receptor or dopamine transporter (DAT) that can disrupt D2-DAT coupling.

Abstract: The present invention provides stable perfluorcarbon nanoemulsions with endocytosis enhancing surfaces that are suitable for gene-transfer, its production and use.

Abstract: The present invention relates to polypeptides having a brain-localizing activity, molecules comprising these polypeptides, and pharmaceutical agents that confer brain-localizing activity. The present inventors are the first to reveal amino acid motif sequences involved in brain-localizing activity. Polypeptides that comprise such motif sequences and have brain localizing activity were discovered as follows: DNAs encoding polypeptides comprising random amino acid sequences were synthesized, and incorporated into a phage library. The phage library produced was used to screen for polypeptides having brain-localized activity, which yielded such several polypeptides. These polypeptides comprised common sequences, which lead to the successful discovery of amino acid motif sequences involved in brain-localizing activity.

Abstract: Provided herein are peptide modulators of ion channels. Specifically, the peptide modulators comprise the amino acid sequence VEDEC wherein V is valine, E is glutamate, D is aspartate, C is cysteine. In certain embodiments, the modulator is attached to the C-terminal end of Slo1 protein isoform. The present invention also claims conjugations of the first valine that make the peptide modulator more membrane permeable, such as myristoyl moieties and arginine-rich cell penetrating peptides. The present invention contemplates use of the peptide modulators in the treatment of diseases/malfunctions such as epilepsy, chronic pain, migraine, asthma, chronic obstructive pulmonary disease, urinary incontinence, hypertension, erectile dysfunction, irritable bowel syndrome, renal disorders of electrolyte imbalance, and possibly in certain kinds of cancer.

Abstract: The present invention is directed to an inventive polymeric carrier molecule according to generic formula (I) and variations thereof, which allows for efficient transfection of nucleic acids into cells in vivo and in vitro, a polymeric carrier cargo complex formed by a nucleic acid and the inventive polymeric carrier molecule, but also methods of preparation of this inventive polymeric carrier molecule and of the inventive polymeric carrier complex. The present invention also provides methods of application and use of this inventive polymeric carrier and the inventive polymeric carrier cargo complex as a medicament, for the treatment of various diseases, and in the preparation of a pharmaceutical composition for the treatment such diseases.

Abstract: This invention relates to the field of antimicrobial agents and more specifically it relates to Efflux Pump Inhibitor (EPI) compounds to be co-administered with antimicrobial agents for the treatment of infections caused by drug resistant pathogens. The EPI compounds are soft drugs which exhibit a reduced propensity for tissue accumulation. The invention includes novel compounds useful as efflux pump inhibitors, compositions and devices comprising such efflux pump inhibitors, and therapeutic use of such compounds.

Abstract: Inhibitors that disrupt binding between a PDZ protein and cognate ligands such as N-methyl-D-aspartate (NMDA) receptors that are involved in various neurological disorders are provided. Pharmaceutical compositions containing such inhibitors and their use in treating neurological diseases such as stroke and ischemia are also disclosed. Screening methods to identify additional inhibitors of specific protein ligand interactions with PDZ proteins are also described.

Abstract: An ophthalmic drug delivery system that contains phospholipid and cholesterol for prolonging drug lifetime in the eyes.

Abstract: The present invention relates to dehydrated nanoparticles comprising chitosan and a nucleic acid. Preferably, the nucleic acid is a siRNA. Dehydrated nanoparticles of the invention have improved storage characteristics. The particles may be used in screening methods, e.g. where they have been dried onto a solid support, such as the surface of a culture well. The nanoparticles may also be dried onto implants for tissue engineering scaffolds, where they enable transfection of cells growing on the scaffold. Moreover, the particles have therapeutic relevance.

Abstract: The present invention relates to stabilized RAP variants and methods of use thereof. Conjugates of stabilized RAP variants to therapeutic compounds and stabilized RAP fusion proteins comprising therapeutic polypeptides are also presented.

Abstract: Disclosed herein are Efflux Pump Inhibitor (EPI) compounds that can be co-administered with antimicrobial agents for the treatment of infections caused by drug resistant pathogens. The EPI compounds are soft drugs which exhibit a reduced propensity for tissue accumulation. It is demonstrated that the EPIs can be used to increase the potency, decrease bacterial resistance and development of bacterial resistance, and increase killing effectivness of tigecycline. Also disclosed are methods of treatment and pharmaceutical compositions for co-administering tigecylcine with an EPI.

Abstract: The present disclosure is directed to methods of administering RL1P76 or an active fragment thereof more than 24 hours after radiation exposure, wherein administration is effective for the protection and treatment of mammals exposed to radiation. In addition, compositions are disclosed including RLIP76 and other radioprotective agents, for example antioxidants.

Abstract: Methods and compositions useful for enhancing the absorption and/or transport of peptides, peptidomimetics, and other gastrointestinal transport protein substrates through gastrointestinal transport proteins are provided. The methods comprise using hormones such as 5-methoxy-N-acetyltryptamine to increase the transport of the peptides, peptidomimetics, and substrates. The compositions comprise one or more hormones and one or more peptides, peptidomimetics, and other gastrointestinal transport protein substrates.

Abstract: The present invention provides a composition and prodrug for targeted drug delivery to the central nervous system of a patient. The inventive composition and prodrug include a pharmaceutically acceptable active agent and at least one protein selected from the group consisting of a fimbrial adhesin protein, a membrane protein, and combinations thereof. The inventive compositions and prodrugs of the present invention selectively target the blood-brain barrier and deliver hydrophilic and lipophilic active agents of varying sizes to the central nervous system.

Abstract: A method comprising orally administering to a mammal a proton pump inhibitor, or a pharmaceutically acceptable prodrug thereof, and a compound which modulates the activity of the MRP2 or other transporter proteins involved in efflux of a proton pump inhibitor or a prodrug, is disclosed herein, said method being effective for the prevention or treatment of a disease or condition related to gastric acid secretion. This method applied to compounds which both inhibit and stimulate MRP2 activity or activity of other transporter proteins involved in efflux of a proton pump inhibitor or a prodrug. Compositions, medicaments, and experimental results related thereto are also disclosed.

Abstract: Based on our identification of a polypeptide (Angiopep-7) that is efficiently transported to cells such as liver, lung, kidney, spleen, and muscle, the invention provides polypeptides, conjugates including the polypeptides, and methods for treating diseases associated with these cell types. Unlike other aprotinin related polypeptides identified herein (including Angiopep-3, Angiopep-4a Angiopep-4b Angiopep-5, and Angiopep-6) which efficiently cross the blood-brain barrier (BBB), Angiopep-7 is not efficiently transported across the BBB.

Abstract: Methods and compositions comprising combinations and uses of a first anti-connexin agent and a second anti-connexin agent, for example, one or more anti-connexin polynucleotides and one or more anti-connexin peptides or peptidomimetics, are provided for therapeutic use including uses for the promotion and/or improvement of wounds and wound healing and/or tissue repair.

Abstract: The technology described herein is directed to conjugating various therapeutic or functional molecules, such small chemical drugs, peptides, oligonucleotides, isotopes and imaging regents with fatty acids, such as LCFAs. The fatty acid-conjugated molecules are complexed with a human serum albumin protein in vitro.

Abstract: The present application discloses a method of treating a disease that is treatable by therapeutic angiogenesis comprising administering to a needy subject an effective amount of a chimeric coiled coil molecule comprising a coiled-coil domain linked to a receptor binding domain of a ligand.

Abstract: This invention relates to a conjugate molecule comprising at least one first portion (I) comprising a carrier sequence and at least one second portion (II) comprising at lest one antitumor drug molecule or a protease inhibitor molecule said conjugate molecule comprising D-enantiomeric amino acids in its portion (I). Furthermore, the invention relates to pharmaceutical compositions containing said conjugate molecule as well as to the use of said conjugate molecule for therapeutic treatment. Methods for improving cell permeability or water solubility are disclosed as well.

Abstract: Methods for inhibiting virus propagation and treating virus infection are provided which include administering to cells infected with viruses a compound capable of inhibiting viral budding from the cells.

Abstract: The disclosure provides elongated nanostructures useful for biological imaging and measurement. More particularly the disclosure provides nanoworms having an increased bioavailability compared to nanospheres.

Abstract: Compositions and methods are provided that include a biologically active agent and a permeabilizing agent effective to enhance mucosal delivery of the biologically active agent in a mammalian subject, in which the permeabilizing peptide is a PN159 analog or conjugate.