Abstract: Methods for treating muscular wasting diseases such as Duchenne muscular dystrophy are disclosed. Specifically, the methods include administering to a subject in need of treatment for a muscular wasting disease, an NF-?B activation inhibitor capable of blocking the activation of NF-?B.

Abstract: The invention relates to a modular transport platform (MTP) configured to penetrate a target cell, deliver the MTP into the target cell, provide a pH dependent membrane disruption activity, direct intracellular transport into a target subcellular compartment of the target cell, and couple the active agent within the modular platform. The modular transport platform includes: (1) a ligand module to target a specific receptor on the surface of the target cell; (2) an endosomolytic module that provides pH-dependent membrane disruption activity within the target cell; (3) an intracellular transport module to cause delivery of the MTP to a particular subcellular compartment; (4) a module for intracellular retention; (5) a module for subcellular recognition; (6) a substance to be transported by the MTP; and (7) a carrier module for unifying the modules and coupling the modules with the transported substance.

Abstract: The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human ?-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.

Abstract: The present invention discloses novel macromolecule transduction domain (MTD) peptides which facilitate the traverse of a biologically active molecule across the cell membrane. Also disclosed are polynucleotides encoding the MTD peptides, methods of identifying the MTD peptides; methods of genetically engineering a biologically active molecule to have cell permeability by using the MTD peptides, methods of importing a biologically active molecule into a cell by using the MTD peptides, and uses thereof.

Abstract: Provided are 9-base morpholino antisense compounds targeted to polyCUG repeats in the 3?UTR region of dystrophia myotonica protein kinase (DMPK) mRNA, and related methods for treating myotonic dystrophy DM1.

Abstract: The present application relates to polypeptides derived from the soluble part of the glycoprotein of the enveloped virus of Primate T-cell leukemia virus (PTLV), or fragments or variants thereof named receptor binding domain ligands (RBD) selected for their ability to bind specifically to the nutrient transporter GLUT1.

Abstract: Aspects of the invention provide methods for selecting a candidate oligonucleotide for activating expression of a target gene. Further aspects of the invention provide methods of selecting a set of oligonucleotides that is enriched in oligonucleotides that activate expression of a target gene. Further aspects provide single stranded oligonucleotides that modulate gene expression and compositions and kits comprising the same. Methods for modulating gene expression using the single stranded oligonucleotides are also provided.

Abstract: The present invention provides compositions and methods for providing factor replacement therapy. In particular, the present invention provides replacement therapy for subjects suffering from cystinosis.

Abstract: A method and compound for treating skeletal muscle mass deficiency in a human subject are disclosed. The composition is an oligomer of morpholino subunits and phosphorus-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5? exocyclic carbon of an adjacent subunit, contains between 10-40 nucleotide bases, has a base sequence effective to hybridize to an expression-sensitive region of processed or preprocessed human myostatin RNA transcript, identified, in its processed form, by SEQ ID NO:6, and is capable of uptake by target muscle cells in the subject. In practicing the method, the compound is administered in an amount and at a dosage schedule to produce an overall reduction in the level of serum myostatin measured in the patient, and preferably to bring the myostatin level within the a range determined for normal, healthy individuals.

Abstract: N-type voltage-gated calcium channels (CaV2.2) are critical mediators of neurotransmitter release and are thought to be involved with transmission of nociception. The use of conventional CaV2.2 blockers in pain therapeutics is limited by side effects. Reported herein is a means to suppress both inflammatory and neuropathic pain without directly blocking CaV2.2, but rather by inhibiting the binding of the axonal collapsin response mediator protein 2 (CRMP-2), a protein known to enhance CaV2.2 function. A 15 amino acid peptide of CRMP-2 fused to the protein transduction domain of the HIV tat protein (TAT CBD3) reduced meningeal blood flow induced by activation of the trigeminovascular system, prevented inflammation-induced tactile hypernociception induced by intraplantar formalin and nocifensive behavior following corneal capsaicin application, and reversed neuropathic hypernociception produced by the antiretroviral drug 2?,3?-dideoxycytidine. Preventing CRMP-2—mediated enhancement of CaV2.

Abstract: Pharmaceutical compositions are provided. The compositions comprise a compound comprising the hyaluronan-containing structure A-(low molecular weight hyaluronan domain)-B. The compositions also comprise a pharmaceutically acceptable excipient. A is hydrogen, a substituent that does not comprise a binding site for tumor necrosis factor stimulated gene-6 (“TSG-6”) protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. B is hydroxyl, a substituent that does not comprise a binding site for TSG-6 protein, a substituent that interferes with binding of TSG-6 protein immediately adjacent thereto, or chondroitin. The composition is suitable for administration by injection, inhalation, topical rub, or ingestion.

Abstract: This invention relates to the use of microcystins as agents for treatment of cancer. Also provided are methods of screening for microcystins with improved cytotoxicity.

Abstract: The present disclosure provides methods and compositions related to the cytosolic delivery of proteins and cell-impermeable small molecules into live cells using an endosomolytic dimer of cell-penetrating peptide TAT.

Abstract: Methods of preparing a proteoliposome comprise the step of contacting a liposome with an effective portion of RalBP1 to create a proteoliposome. RalBP1 is effective for the protection and treatment of mammals and the environment against the accumulation of toxic compounds and prevents accumulation of one or more toxic compounds, reduces the concentration of toxic compounds, and protects against further contamination with one or more toxic compounds.

Abstract: Compositions and methods are provided that are useful for the delivery, including transdermal delivery, of biologically active agents, including nucleic acids and therapeutic proteins including insulin, larger therapeutic proteins such as botulinum toxin and other biologically active agents such as a therapeutic protein which does not therapeutically alter blood glucose levels, a therapeutic nucleic acid-based agent, a non-protein non-nucleic acid therapeutic agent such as an antifungal agent or alternately an agent for immunization. The compositions can be prepared with components useful for targeting the delivery of the compositions as well as imaging components.

Abstract: Provided herein are conjugate molecules containing a substrate for a nucleoside transport pathway linked to an active agent, wherein the conjugate can be transported into a cell or into the nucleus of a cell via a cellular nucleoside transport pathway. Further provided are methods of delivering a conjugate molecule to a target cell expressing a nucleoside transport pathway, wherein the conjugate contains a substrate for the nucleoside transport pathway linked to an active agent. Also provided are methods for screening for conjugates that are transported by nucleoside transport pathways. Further provided are methods of treating a patient having a disease or disorder affecting tissues expressing nucleoside transport pathways, in which a conjugate containing an agent effective in treating the disorder is administered to the patient. Also provided are methods of treating a patient having an autoimmune disorder involving administering to the patient a compound that inhibits a nucleoside transport pathway.

Abstract: The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (pm) and the total number of amino acid residues (r) wherein 3pm is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (pt) wherein 2 a is the largest number that is less than or equal to pt+1, except that when a is 1, pt may also be 1.

Abstract: The peptides of formula (I) R1—(X)K—P—Y, where: R1 is the group attached to the N-terminal of the first amino acid of the sequence P, optionally via the ligand X, and is selected from H, CH3C(?O)—, and maleimide; X is a biradical selected from —NH—(CH2)r—C(?O)—, —C(?O)—(CH2)r—C(?O)—, —S(CH2)r—, —S—(CH2)r—C(?O)—, —O—(CH2)r—, —S—CH2—CH(NH2)—C(?O)—, —O—(CH2)r—C(?O)—, —(CH2)r—C(?O)—, —NH—O—CH2—C(?O)—NH—(CH2)r—CH(NH2)—C(?O)—, —(CH2)r—C(?O)—NH—(CH2)r—CH(NH2)—C(?O)—, and —NH—(CH2)r—CH(NHC(?O)CH2NH2)—C(?O)—; r is 1-5; P is a biradical of an amino acid sequence comprising the sequence D-Pro-D-Trp-D-Val-D-Pro-D-Ser-D-Trp-D-Met-D-Pro-D-Pro-D-Arg-D-His-D-Thr (SEQ ID NO: 1); Y is the group attached to the C-terminal of the last amino acid of the sequence P, and is selected from —NH2, —OH, —OR2 and —NHR2; R2 is a radical selected from (C1-C6)-alkyl and (CH2)2—NH—C(?O)—CH2—O—NH2; k is 0-2; m is 0-1; with the proviso that when the biradical X is —C(?O)(CH2)rC(?O)—, then R1 is H; when the N of the amino acid of the sequence P

Abstract: The present invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum wherein (i) the protein binds specifically to nerve cells with a higher or lower affinity as the native neurotoxin; (ii) the protein has an increased or reduced neurotoxicity compared to the native neurotoxin, the neurotoxicity being preferably determined in the hemidiaphragm assay; and/or (iii) the protein comprises a lower affinity against neutralizing antibodies compared to the native neurotoxin. The invention also relates to methods for producing the same and the use thereof in cosmetic and pharmaceutical compositions.

Abstract: Methods of preparing a proteoliposome comprise the step of contacting a liposome with an effective portion of RalBP1 to create a proteoliposome. RalBP1 is effective for the protection and treatment of mammals and the environment against the accumulation of toxic compounds, and prevents accumulation of one or more toxic compounds, reduces the concentration of toxic compounds, and protects against further contamination with one or more toxic compounds. In addition, RalBP1 is effective for the protection and treatment of mammals against the effects of ionizing radiation.

Abstract: Provided herein are methods of preventing or reducing the effects of exposure to a mustard compound. The methods include the steps of contacting cells exposed to a mustard compound or at risk of exposure to a mustard compound with a composition comprising a polypeptide comprising RLIP76 or an active fragment or variant thereof. Optionally, the methods include the steps of administering to a subject exposed to a mustard compound or at risk of exposure to a mustard compound a composition comprising a polypeptide comprising RLIP76 or an active fragment or variant thereof.

Abstract: The invention provides a recombinant polypeptide X-Y for enhancing cell transduction efficiency of a target agent, wherein X is a cell penetrating peptide DPV3, and Y is an Hsp40-J domain. Also provided is a method for enhancing cell transduction efficiency of a target agent, comprising conjugating/attaching said target agent with a recombinant polypeptide X-Y, wherein X is a cell penetrating peptide DPV3, and Y is an Hsp40-J domain. Further provided is a pharmaceutical composition comprising a therapeutic agent, wherein said therapeutic agent is modified by conjugating/attaching with a recombinant polypeptide X-Y, wherein X is a cell penetrating peptide DPV3, and Y is an Hsp40-J domain.

Abstract: The invention provides fusion protein constructs comprising a functional mitochondrial protein and methods of treating mitochondrial disorders by the fusion proteins and compositions thereof.

Abstract: Described herein are methods of delivering a nanoparticle to the brain of a subject by administering to the subject a nanoparticle having a nanoparticle core and a targeting agent. A variety of targeting agents may serve to promote delivery of the described nanoparticle. For example, the targeting agent may include a ligand specific for a receptor expressed by brain endothelial cells and a linker that connects the ligand to the external surface of the nanoparticle core. Additionally, the linker can promote disassociation of the ligand from the nanoparticle when inside a cell.

Abstract: Functionalized biocompatible nanoparticles capable of penetrating through a mammalian cell membrane and delivering intracellularly a plurality of bioactive molecules for modulating a cellular function are disclosed herein The functionalized biocompatible nanoparticles comprise: a central nanoparticle ranging in size from about 5 to about 50 nm and having a polymer coating thereon, a plurality of functional groups covalently attached to the polymer coating, wherein the plurality of bioactive molecules are attached to the plurality of the functional groups, and wherein the plurality of bioactive molecules include at least a peptide and a protein, and wherein the peptide is capable of penetrating through the mammalian cell membrane and entering into the cell, and wherein the protein is capable of providing a new functionality within the cell. The protein may be a transcription factor selected from the group consisting of Oct4, Sox2, Nanog, Lin28, cMyc, and Klf4.

Abstract: A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.

Abstract: Devices and methods for treating diseases associated with loss of neuronal function are described. The methods are designed to promote proliferation, differentiation, migration, or integration of endogenous progenitor stem cells of the central nervous system (CNS). A therapy, such as an electrical signal or a stem cell enhancing agent, or a combination of therapies, is applied to a CNS region containing endogenous stem cells or a CNS region where the endogenous stem cells are predicted to migrate and eventually reside, or a combination thereof.

Abstract: Provided is a cyclic peptide which comprises: (i) a CDK4 peptide region; and (ii) a cell-penetrating region; wherein the CDK4 peptide region comprises the amino acid sequence P1R1x1y1R2P2V (SEQ ID NO: 1), in which P1 and P2 are each proline, R1 and R2 are each arginine and each of x1 and y1 are either a linker or proline, wherein if x1 is a linker then y1 is proline or if x1 is proline then y1 is a linker, or wherein x1 and y1 when taken together form a linker, and wherein V may be present or absent; and wherein the cell-penetrating region is capable of enhancing the uptake of the cyclic peptide or a part thereof into cancer cells and comprises an amphiphilic amino acid sequence; and wherein the cyclic peptide or a part thereof is cytotoxic to and/or inhibiting to the growth of a cancer cell.

Abstract: The present invention relates to an improved macromolecule transduction domain (MTD), which facilitates permeating the cell membrane of a biologically active molecule, having enhanced cell permeability. Specifically, an improved MTD according to the present invention, compared to an existing MTD, can transmit various types of biologically active molecule from inside the body and inside a test tube more effectively, and thus can be effectively used in a method to genetically alter a biologically active molecule so as to have cell permeability or in a method to transport a biologically active molecule into a cell, or the like. Additionally, the improved MTD can be very useful in development of new drugs and incrementally modified drugs as uses of the improved MTD are possible in drug delivery systems, recombinant protein vaccines or DNA/RNA therapeutic agents, gene or protein therapies, and pharmacologically or medically useful protein production or medical, pharmacological and pharmaceutical compositions.

Abstract: The present disclosure provides pyrimidine diol amides of Formula (I), and the pharmaceutically acceptable solvates and prodrugs thereof, wherein A1, X, A2, W1, W2, W3, R1, R2, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.

Abstract: The present invention relates to a WNT-derived novel peptide and use thereof. WNT-derived peptide of the present invention possesses identical or similar activities to natural-occurring WNT protein, and has much higher stability and skin penetration potency than natural-occurring WNT protein. Therefore, the composition containing the present peptide not only shows excellent effects on improvement in hair loss (for example, promotion of hair growth or production of hair), but also has superior efficacies on treatment of a WNT signal transduction pathway-related disorder. In addition, the outstanding activity and stability of the present peptide described above may be greatly advantageous in application to pharmaceutical compositions, quasi-drugs and cosmetics.

Abstract: A nanoparticle-polypeptide complex comprising a bioactive polypeptide in association with a nanoparticle, wherein the bioactive polypeptide is modified by the addition of a chemical moiety that facilitates cellular uptake of the protein. The polypeptide can be a protein or a peptide. In some embodiments, the amino acid sequence of the protein or peptide is derived from the amino acid sequence of a tumor suppressor gene product.

Abstract: The present invention provides a method for ameliorating inflammatory and/or neuropathic pain in a subject by modifying the activity of N-methyl-D-aspartate (NMDA) receptors in cells of the subject by inhibition of the interaction of the unique domain of the tyrosine kinase Src enzyme and the NMDA receptor complex.

Abstract: Provided are methods and compositions, including topical compositions, for inducing tolerance to a sensitizing agent known to provoke contact hypersensitivity in a subject. Included are methods of topically applying to the subject an effective amount of an antisense composition targeting the start site or splice site of a CFLAR mRNA.

Abstract: The present disclosure relates generally to novel methods and compositions for using engineered reprogramming factor(s) for the creation of induced pluripotent stem cells (iPSCs) through a kinetically controlled process. Specifically, this disclosure relates to establishing combinations of reprogramming factors, including fusions between conventional reprogramming factors with transactivation domains, optimized for reprogramming various types of cells. More specifically, the exemplary methods disclosed herein can be used for creating induced pluripotent stem cells from various mammalian cell types, including human fibroblasts. Exemplary methods of feeder-free derivation of human induced pluripotent stem cells using synthetic messenger RNA are also disclosed.

Abstract: A compound including a cell penetrating peptide (CPP), an elastin-like polypeptide (ELP), and a therapeutic peptide (TP) can be preferentially directed to a target site by applying hyperthermia. The compound can be useful for the treatment of tumors.

Abstract: The pharmaceutical composition includes at least one pharmaceutically acceptable carrier, and an active ingredient including an artificially synthesized peptide includes: (A) an amino acid sequence constituting a cell-penetrating peptide and (B) an amino acid sequence constituting the signal peptide in amyloid precursor protein (APP) or an N-terminal partial amino acid sequence or C-terminal partial amino acid sequence from the amino acid sequence constituting that signal peptide.

Abstract: A chlorotoxin conjugate detectable by fluorescence imaging that allows for intra-operative visualization of cancerous tissues, compositions that include the chlorotoxin conjugate, and methods for using the chlorotoxin conjugate.

Abstract: Compositions that facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells are provided. In some embodiments, the compositions include a peptide, an active agent, and a carrier that includes the active agent, wherein the peptide has an amino acid sequence set forth in any of SEQ ID NOs: 1-18; the peptide is associated with and/or conjugated to the active agent, the carrier, or both; the carrier is selected from the group consisting of a micelle, a liposome, an ethosome, and combinations thereof; and the composition is capable of penetrating a stratum corneum (SC) layer when contacted therewith or penetrating a cell when contacted therewith, and optionally wherein the composition further includes one or more free peptides having an amino acid sequence set forth in any of SEQ ID NOs: 1-18.

Abstract: A nucleic acid is effectively introduced into a cell while suppressing the cytotoxicity by administering a nucleic acid complex comprising a high molecular weight derivative of ?-poly-L-lysine and a nucleic acid to a cell.

Abstract: The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

Abstract: The present invention is directed to compositions and methods for treating immune system mediated disease. In particular, certain embodiments of the present invention use BH3 mimetic therapy as an efficacious treatment of the effector phase of RA wherein the compositions and methods of the present invention markedly reduce the level of the Bcl-2 antagonist protein Bim present in RA synovial tissue as compared to control patients. Therefore, the present invention involves restoring the function of Bim in order to ameliorate inflammatory arthritis. In connection therewith, systemic delivery of a peptide to the BH3 domain of Bim effectively inhibits the development of K/B×N serum transfer-induced arthritis which closely resembles the effector phase of RA.

Abstract: Methods and pharmaceutical compositions for the treatment of cancer or acute ischemia are provided. Also provided are methods of identifying agents capable of preventing the formation of or dissociating the MSF-A-HIF-1alpha protein complex, and methods of determining the prognosis of an individual having cancer by identifying the presence or absence of such a protein complex.

Abstract: Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.

Abstract: A peptide-POD with ability to penetrate and deliver fluorophores, siRNA, DNA and quantum dots to cells in culture and retinal and ocular tissues in vivo is provided herein. POD couples to adenovirus vectors, enhancing tropism for certain cells, potentially providing a safer and more efficacious method to deliver molecules to ocular and other tissues in vivo. POD constructs are therapeutic delivery vehicles for treating cells and tissues, including ocular cells and tissues suffering from retinal degeneration.

Abstract: Methods and compositions for treating an iron disorder in a patient are presented, including methods for delivering a therapeutically effective amount of iron to the brain. Iron disorders that may be treated by these methods include iron deficiency disorders and iron overload disorders. A recombinant yeast expressing human H-ferritin and a composition for treating an iron disorder comprising this recombinant yeast are also presented.

Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8.

Abstract: The embodiment of the invention is a virus-like particle vector, a process for the manufacture thereof, use of the virus-like particle vector and a pharmaceutical composition, which contains the virus-like particle vector. The vector is intended for the delivery of therapeutic agents into specific mammalian tissues, especially low molecular weight agents, in particular low molecular weight anti-cancer drugs into cancer tissues. More specifically, the invention relates to the virus-like particle vector, which constitutes an adenoviral dodecahedron with the therapeutic substance encapsulated or covalently linked.

Abstract: An object of the present invention is to provide a substance which is able to be an active ingredient for the improvement of dysfunction caused by nerve damage. An improving agent for dysfunction due to nerve damage of the present invention as a means for resolution thereof is characterized in that it comprises an endo-?-N-acetylglucosaminidase type enzyme which hydrolyzes an N-acetylglucosamide bond in a keratan sulfate backbone as an active ingredient. When the improving agent of the present invention is administered, clinical improvement is achieved in motor neuron dysfunction and sensory neuron dysfunction such as neuropathic pain represented by a pain caused by allodynia and hyperalgesic reaction of the object to be treated.

Abstract: Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.