Abstract: The present disclosure provides meroduplex (nicked or gapped) ribonucleic acid molecules (mdRNA) that decreases or silences target 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 target gene RNA. In addition, the meroduplex may have one or more modifications or substitutions, such as nucleotide base, sugar, terminal cap structure, internucleotide linkage, or any combination of such modifications. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease related to altered expression of a 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: The present disclosure provides meroduplex (nicked or gapped) ribonucleic acid molecules (mdRNA) that decreases or silences target 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 target gene RNA. In addition, the meroduplex may have one or more modifications or substitutions, such as nucleotide base, sugar, terminal cap structure, internucleotide linkage, or any combination of such modifications. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease related to altered expression of a target gene.

Abstract: A serum-stable mixture of lipids capable of encapsulating an active agent to form a liposome, said mixture comprising phosphatidylcholine and phosphatidylethanolamine in a ratio in the range of about 0.5 to about 8. The mixture may also include pH sensitive anionic and cationic amphiphiles, such that the mixture is amphoteric, being negatively charged or neutral at pH 7.4 and positively charged at pH 4. Amphoteric liposomes comprising such a mixture may be used for encapsulating nucleic acid therapeutics, such as oligonucleotides and DNA plasmids. The drug/lipid ratio may be adjusted to target the liposomes to particular organs or other sites in the body.

Abstract: Methods are described for the delivery of one or more small interfering RNAs (siRNAs) to a eukaryotic cell using a bacterium or BTP. Methods are also described for using this bacterium to regulate gene expression in eukaryotic cells using RNA interference, and methods for treating viral diseases and disorders. The bacterium or BTP includes one or more siRNAs or one or more DNA molecules encoding one or more siRNAs. Vectors are also described for use with the bacteria of the invention for causing RNA interference in eukaryotic cells.

Abstract: Synthesis and uses of conformationally restricted nucleomonomers (CRN) to prepare nucleic acid compounds. Methods for preparing nucleomonomers for nucleic acid compounds in high yields and in multi-gram scale for therapeutic modalities useful for treating or preventing diseases or disorders by up- or down-regulating the expression of genes and other nucleic acid based regulatory systems in a cell.

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: This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: The invention suggests amphoteric lipids wherein one or more amphoteric groups having an isoelectric point between 4 and 9 are substituted on a membranous or membrane-forming amphiphilic substance, as well as liposomes containing such compounds.

Abstract: An amphoteric liposome comprising neutral lipids wherein said neutral lipids are selected from the group comprising cholesterol or mixtures of cholesterol and at least one neutral or zwitterionic lipid and wherein K (neutral) of said mixtures is 0.3 or less. Said amphoteric liposome may encapsulate an active agent, such as nucleic acid therapeutics. Also disclosed are pharmaceutical compositions comprising said amphoteric liposomes as a carrier for the delivery or targeted delivery of active agents or ingredients.

Abstract: A method for preparing amphoteric liposomes loaded with a polyanionic active agent as cargo, characterised by admixing an aqueous solution of said polyanionic active agent and an alcoholic solution of one or more amphiphiles and buffering said admixture to an acidic pH, said one or more amphiphiles being susceptible of forming amphoteric liposomes at said acidic pH, thereby to form such amphoteric liposomes in suspension encapsulating said active agent under conditions such that said liposomes form aggregates, and thereafter treating said suspension to dissociate said aggregates. Also disclosed are nucleic acid loaded amphoteric liposomes produced in accordance with the method, wherein said nucleic acids are oligonucleotides and said liposomes are multilamellar.

Abstract: This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: The invention suggests amphoteric lipids wherein one or more amphoteric groups having an isoelectric point between 4 and 9 are substituted on a membranous or membrane-forming amphiphilic substance, as well as liposomes containing such compounds.

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: This disclosure provides a range of amino acid lipid compounds and compositions useful for drug delivery, therapeutics, and the diagnosis and treatment of diseases and conditions. The amino acid lipid compounds and compositions can be used for delivery of various agents such as nucleic acid therapeutics to cells, tissues, organs, and subjects.

Abstract: This disclosure provides single-stranded and multi-stranded nucleic acid compounds having one or more double-stranded regions that regulate the function or expression of nucleic acid molecules expressed in a cell or a cell regulatory system dependent upon a nucleic acid. The disclosure provides a range of nucleic acid compounds having one or more conformationally restricted nucleomonomers (CRN). Certain nucleic acid compounds may have one or more conformationally restricted nucleomonomers and one or more hydroxymethyl substituted nucleomonomers (UNA). The nucleic acid compounds are useful in various therapeutic modalities.

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: Compounds comprising condensed particles having diameters less than 1000 nm, wherein the particles comprise one or more double stranded ribonucleic acids (dsRNAs) and one or more peptides. The compounds, compositions and methods are useful for modulating gene expression by RNA interference.

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.

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.