Abstract: The present disclosure provides RNA molecules, for example, meroduplex ribonucleic acid molecules (mdRNA), and blunt ended double-stranded ribonucleic acid molecules capable of decreasing or silencing expression of a target gene. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target mRNA. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease or condition associated with the target gene.

Abstract: A delivery-enhancing peptide comprising the amino acid sequence of SEQ ID NO:11 or salt thereof. This invention is directed towards methods and compositions to administer a double-stranded ribonucleic acid to a mammal so as to effectuate transfection of the double-stranded RNA into a desired tissue of the mammal.

Abstract: Methods and compositions containing oxytocin or an oxytocin analog, such as carbetocin, are provided for the prevention and treatment of autism spectrum disorders, related disorders and symptoms of such disorders. The methods and compositions of this disclosure are effective in the treatment of social withdrawal, eye contact avoidance, repetitive behaviors, anxiety, attention deficit, hyperactivity, depression, loss of speech, verbal communication difficulties, aversion to touch, visual difficulties, comprehension difficulties, and sound and light sensitivity. Additional compositions and methods are provided which employ oxytocin or an oxytocin analog in combination with a secondary or adjunctive therapeutic agent to yield more effective treatment tools against autism spectrum disorders and related disorders.

Abstract: Lipopeptide compounds comprising a peptide having 2 to 100 amino acid residues, and having a lipophilic group attached to at least one terminus of the peptide or to at least one amino acid residue of the peptide, and salts and uses thereof. The lipophilic group may be attached to the N-terminus, C-terminus or both termini of the peptide. The lipophilic group may be attached to at least one interal amino acid residue (i.e., an amino acid residue that is not the N-terminus or the C-terminus amino acid residue of the peptide). The lipophilic group may be attached to either termini or both and at least one internal amino acid residue.

Abstract: What is described are pharmaceutical compositions, formulations, and uses thereof, for medicaments for intranasal delivery of insulin to a patient, comprising an aqueous mixture of human insulin, a solubilizing agent, and a surface active agent, wherein the human insulin may be rapid actin insulin.

Abstract: This disclosure provides the construction, expression, and selection of the mutated genes that encode novel Trp cage polypeptides with desirable binding properties, as well as the novel Trp cage polypeptides themselves. The substances or targets bound by these novel Trp cage polypeptides may be but need not be proteins or polypeptides. Targets may include other biological or synthetic macromolecules as well as other organic and inorganic substances. Further, targets may also include a single or multiple cell or tissue types. The present invention achieves genetic variants of Trp cage-encoding nucleic acids through controlled random mutagenesis of the nucleic acids yielding a mixture of Trp cage polypeptides that are capable of binding targets.

Abstract: Pharmaceutical compositions and methods are described comprising at least a parathyroid hormone peptide (PTH) preferably PTH1-34 and one or more mucosal delivery-enhancing agents for enhanced nasal mucosal delivery of PTH, for treating or preventing osteoporosis or osteopenia in a mammalian subject, preferably a human.

Abstract: What is described is an aqueous pharmaceutical composition for intranasal delivery of PTH, comprising a PTH molecule, and one or more excipients selected from the group consisting of a chelating agent, an alcohol, and a surface active agent, wherein the PTH molecule selected from the group consisting of SEQ NO: 1, SEQ NO: 2, and SEQ NO: 3.

Abstract: Double stranded siRNA molecules for combatting a respiratory virus, wherein the strands of an siRNA molecule may be from about 15 to about 60 nucleotides, and uses thereof. One strand of an siRNA molecule can be a nucleic acid sequence identical to a conserved site, or a variant thereof, within the nucleic acid sequence of the respiratory virus.

Abstract: This disclosure provides the construction, expression, and selection of the mutated genes that encode novel Trp cage polypeptides with desirable binding properties, as well as the novel Trp cage polypeptides themselves. The substances or targets bound by these novel Trp cage polypeptides may be but need not be proteins or polypeptides. Targets may include other biological or synthetic macromolecules as well as other organic and inorganic substances. Further, targets may also include a single or multiple cell or tissue types. The present invention achieves genetic variants of Trp cage-encoding nucleic acids through controlled random mutagenesis of the nucleic acids yielding a mixture of Trp cage polypeptides that are capable of binding targets.

Abstract: Processes and compositions for liposomal delivery of therapeuticals prepared by contacting an aqueous solution of an active agent with a solution of liposome-forming components containing one or more DILA2 amino acid compounds or lipids in organic solvent to form an impinging stream. A protocol including flow rates, pH, and an incubation period are used to control formation of liposomal components for therapeutic applications. The impinging stream may be collected and incubated to prepare a liposomal formulation which encapsulates the active agent. The composition can be quenched with buffer and filtered by tangential flow and diafiltration and other means for finishing as a pharmaceutical composition. An efficiency for delivering a drug cargo is provided.

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing one or more ERBB family gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to one or more ERBB family mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine and optionally other modifications or combinations thereof. Also provided are methods of decreasing expression of one or more ERBB family gene in a cell or in a subject to treat one or more ERBB family-related disease.

Abstract: The present disclosure provides RNA molecules, for example, meroduplex ribonucleic acid molecules (mdRNA), and blunt ended double-stranded ribonucleic acid molecules capable of decreasing or silencing expression of a target gene. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target mRNA. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease or condition associated with the target gene.

Abstract: The present disclosure relates to the construction, expression, and selection of genes that encode novel Trp cage polypeptides with desirable cell and/or tissue binding properties, as well as the novel Trp cage polypeptides themselves. A polypeptide of this disclosure may contain all or part of amino acid sequence AAADX1YX2QWLX3X4X5GPX6SGRPPPX7 (SEQ ID NO: 4), wherein Xn represents an amino acid found in position n, the polypeptide comprising a tryptophan cage (Trp cage).

Abstract: The use of antagonists to JAM-1 Claudin-4 and occludin to open tight junctions. The antagonists include, by way of example antibodies and antibody fragments that bind to the proteins and small interfering nucleic acids that downregulate the mRNA encoding the proteins.

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing RAS (e.g., HRAS, KRAS, NRAS) gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to an HRAS, KRAS, or NRAS mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a RAS gene in a cell or in a subject to treat a RAS-related disease.

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing MYC gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-over-lapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a MYC mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine, a nucleoside replaced with a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a MYC gene in a cell or in a subject to treat a MYC-related disease.

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing WNT1, WNT2, or WNT3A gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a WNT1, WNT2, or WNT3A mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a WNT1, WNT2, or WNT3A gene in a cell or in a subject to treat a WNT1, WNT2, or WNT3A-related disease.

Abstract: The present invention is directed to RNA oligonucleotides or complexes of RNA oligonucleotides, denoted herein together as RNA complexes, containing at least one, but optionally more that one, hydroxymethyl substituted nucleotide monomer(s). By a hydroxymethyl substituted nucleotide monomer is understood a nucleotide monomer containing a hydroxymethyl group (that may be unsubstituted, O-substituted for example with a conjugating group, or converted into an optionally substituted or conjugated aminomethyl group). This hydroxymethyl group is not partaking in formation of an internucleotide linkage and is not the hydroxymethyl group (containing the 5?-hydroxy group) of a natural RNA monomer. The RNA complexes of the invention may be useful for therapeutic applications, diagnostic applications or research applications.

Abstract: The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing one or more VEGF family gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to one or more VEGF family mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine and optionally other modifications or combinations thereof. Also provided are methods of decreasing expression of one or more VEGF family gene in a cell or in a subject to treat one or more VEGF family-related disease.