Abstract: The present invention relates to methods for in vivo administration of sd-rxRNA molecules.

Abstract: Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

Abstract: Methods and systems are provided for a systematic approach to computer aided inventing. In a modeling environment, a model representing an item, composition or process can be defined and configured using the lexicon and specification of an innovation database. In the model, objects can be indentified, defined, and configured to provide the model with constituent products, components, features and materials. An innovation engine automatically applies one or more morphs from the innovation database to the objects or the model to generate morphed versions of the model that may provide innovations of, or invention to, the item, composition or process represented by the model.

Abstract: The invention relates to liquid containers comprising a plurality of sealed additive chambers in communication with a vessel fillable with a liquid. The additive chambers comprise independently selected additives that may be added to a liquid in the container at the option of the user. The user can manually open the additive chambers of their choice and release the additive into a liquid in the vessel without destroying the integrity of the container. In this manner, the liquid containers are programmable by the users and various aspects of the liquid in the container, such as color and/or flavor, is controlled by the user.

Abstract: Methods and systems are provided for a systematic approach to computer aided inventing. In a modeling environment, a model representing any item, composition or process can be defined and configured using the lexicon and specification of an innovation database. In the model, objects can be identified, defined, and configured to provide the model with constituent products, components, features and materials. An innovation engine automatically applies one or more morphs from the innovation database to the objects of the model to generate morphed versions of the model that may provide innovations of or invention to the item, composition or process represented by the model.

Abstract: Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

Abstract: The present invention relates to RNAi constructs and their use in gene silencing. RNAi constructs associated with the invention contain a double stranded region connected to a single stranded region of phosphorothioate modified nucleotides.

Abstract: RNAi constructs directed to MAP4K4 that demonstrate unexpectedly high gene silencing activities, and uses thereof are disclosed. The blunt-ended constructs have a double-stranded region of 19-49 nucleotides. The constructs have selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the strands may be modified (e.g., one or both ends of the sense strand is modified by 2?-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, the antisense strand may also be modified by a 2?-O-methyl group at the penultimate 5?-end nucleotide to greatly reduce off-target silencing.

Abstract: The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.

Abstract: The present invention provides a particulate delivery system for delivering an RNAi construct to phagocytic cells such as macrophages, comprising various configurations of a complex comprising a phagocytic cell-targeting moiety and an RNAi construct. The invention further provides methods of making the delivery system, and their uses, such as treating phagocytic cell-associated disease conditions.

Abstract: The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing. The RNAi constructs may be, for instance, miRNA constructs that are miRNA modulators.

Abstract: The invention relates to improved double-stranded RNAi constructs (sometimes referred to as “solo-rxRNA”) and uses thereof. The construct comprises a structure formed in some aspects of the invention by two identical single-stranded polynucleotides, with the structure having two double-stranded stem regions (each having less than 21 base pairs) and a loop or bulge having about 4 to 11 nucleotides on each strand. The construct is resistant to cleavage by Dicer or other Dicer-like RNase III enzymes and is capable of being loaded into a RISC complex to effect RNA interference. In addition, the nucleotides of the present hairpin constructs may be modified to greatly enhance functionality, such as stability and specificity.

Abstract: The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

Abstract: Neutral lipid formulations for nucleic acid delivery are provided according to the invention. The neutral lipid formulations include hydrophobically modified polynucleotides and fat mixtures. Methods of using the neutral lipid formulations are also provided.

Abstract: Methods and systems are provided for a systematic approach to computer aided inventing. In a modeling environment, a model representing any item, composition or process can be defined and configured using the lexicon and specification of an innovation database. In the model, objects can be identified, defined, and configured to provide the model with constituent products, components, features and materials. An innovation engine automatically applies one or more morphs from the innovation database to the objects of the model to generate morphed versions of the model that may provide innovations of or inventions to the item, composition or process represented by the model.

Abstract: The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2?-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2?-O-methyl group at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

Abstract: The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

Abstract: Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

Abstract: The invention relates to machine-readable code that tracks user input and associated computer output during use of a computer programmed with the code, identifies repetitive patterns and automates the user input portion of those identified repetitive patterns when they occur again.

Abstract: The invention relates to liquid containers comprising a plurality of sealed additive chambers in communication with a vessel tillable with a liquid. The additive chambers comprise independently selected additives that may be added to a liquid in the container at the option of the user. The user can manually open the additive chambers of their choice and release the additive into a liquid in the vessel without destroying the integrity of the container. In this manner, the liquid containers are programmable by the users and various aspects of the liquid in the container, such as color and/or flavor, is controlled by the user.