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 present disclosure relates to RNAi constructs with improved cellular uptake characteristics and methods of use of these compounds for silencing expression of long coding RNAs (IncRNAs).

Abstract: The invention pertains to the use of therapeutic approaches to treat various skin disorders and conditions. In particular, the invention pertains to the treatment of cutaneous cancers and cutaneous metastasis of solid tumors, as well as to the removal of tattoos, using a hapten. The invention provides various topical formulations comprising a hapten for treatment of these skin disorders and conditions.

Abstract: The invention relates to various PCSK9 RNAi constructs with gene silencing activities, 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. The sense strand may be modified 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 groups at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target 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 and fibrotic 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: 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 present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

Abstract: The present invention relates to methods and compositions for the treatment of alopecia areata. In some aspects, the present invention relates to haptens for use in treating alopecia areata. In other aspects, the present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds the treatment of alopecia areata. In other aspects, the present invention relates to compositions comprising haptens formulated as gels or ointments.

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: In one aspect, the disclosure provides methods for treating a neurodegenerative disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a nucleic acid molecule and a therapeutically effective amount of a small molecule that activates NF-?B p65 and increases expression of manganese superoxide dismutase (MnSOD/SOD2) and/or expression of a related protein or enzyme.

Abstract: Aspects of the invention relate to methods for treating ALS comprising administering to a subject in need thereof a therapeutically effective amount of a nucleic acid molecule that is directed against a gene encoding superoxide dismutase 1 (SOD1).

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

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: 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: 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: The invention relates to various PCSK9 RNAi constructs with gene silencing activities, 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. The sense strand may be modified 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 groups at the 2nd 5?-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target 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 and fibrotic applications.

Abstract: Aspects of the invention relate to methods for treating an ocular disorder associated with the front of the eye, comprising administering to the eye of a subject in need thereof a therapeutic RNA molecule, in an effective amount to treat an ocular disorder associated with the front of the eye.