Abstract: Compositions and methods useful in administering nucleic acid based therapies, for example association complexes such as liposomes and lipoplexes are described.

Abstract: The present invention provides compounds of formula (1). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and methods of treating subjects having a bleeding disorder, such as a hemophilia.

Abstract: The present invention provides effective motifs for RNA agents conjugated to at least one ligand, which are advantageous for the in vivo delivery of iRNA duplex agents. Additionally, the present invention provides methods of making these compositions, as well as methods of introducing these iRNA duplex agents into cells using these compositions, e.g., for the treatment of various disease conditions.

Abstract: The invention relates to compositions and methods for site-specific delivery of nucleic acids by combining them with targeting ligands and endosomolytic components.

Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

Abstract: This invention relates generally to chemically modified oligonuceotides useful for modulating expression of microRNAs and pre-microRNAs. More particularly, the invention relates to single stranded chemically modified oligonuceotides for inhibiting microRNA and pre-microRNA expression and to methods of making and using the modified oligonucleotides. Also included in the invention are compositions and methods for silencing microRNAs in the central nervous system.

Abstract: The present invention relates to multifunctional polymers represented by the following formula: The invention further provides methods for their preparation and methods for site-specific delivery of nucleic acids by combining them with targeting ligands, endosomolytic ligands and/or PK modulator ligands.

Abstract: The present invention provides iRNA agent including at least one monomer having the structure shown in formula (I?) wherein: A and B are each independently for each occurrence O, N(RN) or S; X is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z?)(Z?)O-nucleoside, —P(Z?)(Z?)O-oligonucleotide, a lipid, a PEG, a steroid, a polymer, —P(Z?)(Z?)O-L6-Q?-L7-OP(Z??)(Z???)O-oligonucleotide, a nucleotide, or an oligonucleotide; Y is H, a protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z?)(Z?)O-nucleoside, —P(Z?)(Z?)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z?)(Z?)O-L6-Q?-L7-OP(Z??)(Z???)O-oligonucleotide, a nucleotide, or an oligonucleotide; R is folate, a folate analog a folate mimic or a folate receptor binding ligand; L6 and L7 are each independently for ea

Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.

Abstract: A targeting lipid can have the formula (I) in which T4 is a targeting moiety. The targeting moiety can be chosen to favor the lipid being localized with a desired organ, tissue, cell, cell type or subtype, or organelle. The targeting moiety can include, for example, transferrin, anisamide, an RGD peptide, prostate specific membrane antigen (PSMA), fucose, an antibody, or an aptamer.

Abstract: The present invention provides nucleosides of formula (1) and oligonucleotides comprising at least on nucleoside of formula (2):Formula (1) and Formula (2). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.

Abstract: The present invention provides single-stranded and double-stranded oligonucleotides comprising at least one aralkyl ligand that improvise the pharmacokinetic properties of the oligonucleotide. The aralkyl ligands of the present invention include naproxen, ibuprofen, and derivatives thereof. The present invention also provides method for modulating gene expression using the modified oligonucleotide compounds and compositions comprising those modified oligonucleotides.

Abstract: The present invention provides compositions comprising a nucleic acid lipid particle and an oligomeric compound and uses thereof. In certain embodiments, such compositions are useful as antisense compounds. Certain such antisense compounds are useful as RNase H antisense compounds or as RNAi compounds.

Abstract: This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene.

Abstract: The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z?)(Z?)O-nucleoside, —P(Z?)(Z?)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z?)(Z?)O-Linker-OP(Z??)(Z??)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z?)(Z?)-formula (I), —P(Z?)(Z?)— or -Linker-R; R is LG, -Linker-LG, or has the structure shown below: LG is independently for each occurrence a carbohydrate, e.g.

Abstract: This invention relates to acyclic and abasic nucleosides and oligonucleotides prepared therefrom. For instance, oligonucleotides can be prepared having one or more of the following formulas (I-III):, or isomers thereof.

Abstract: A lipid particle can include a cationic lipid. Synthesis of the cationic lipid can include a ylide-based reaction, such as a Wittig reaction or sulfur ylide reaction. In some cases, the synthesis can also include a Michael addition or a related addition reaction.

Abstract: Provided herein are modified 5? diphosphate nucleosides and oligomeric compounds prepared therefrom. More particularly, modified 5? diphosphate nucleosides are provided that can be further modified at the 2? and 5? positions. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The oligomeric compounds are also expected to be useful as primers and probes in diagnostic applications.

Abstract: The present invention relates to processes and reagents for oligonucleotide synthesis and purification. One aspect of the present invention relates to compounds useful for activating phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to a method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups.