Abstract: The present application relates to compositions and methods for modulating expression of Family with Sequence Similarity 13 Member A (FAM13A) protein. In particular, the present application relates to nucleic acid-based therapeutics for reducing FAM13A gene expression via RNA interference and methods of using such nucleic acid-based therapeutics to reduce abdominal adiposity, reduce body weight, reduce fat mass, improve metabolic parameters including insulin resistance and non-alcoholic steatohepatitis (NASH), and reduce risk of myocardial infarction.

Abstract: The present invention relates to RNAi constructs for reducing expression of the HSD17B13 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the SCAP gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the MARC1 gene. Methods of using such RNAi constructs to treat or prevent liver fibrosis and fatty liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, are also described.

Abstract: The present invention relates to chemically-modified RNAi constructs for reducing expression of a target gene. In particular, the invention relates to specific patterns of modified nucleotides to be incorporated into RNAi constructs to improve in vivo stability and efficacy. Also described are pharmaceutical compositions comprising the chemically-modified RNAi constructs and methods of inhibiting target gene expression in vivo by administering the chemically-modified RNAi constructs, for example, to treat or ameliorate various disease conditions.

Abstract: The present invention relates to RNAi constructs for reducing expression of the PNPLA3 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the PNPLA3 gene. Methods of using such RNAi constructs to treat or prevent liver disease, nonalcoholic fatty liver disease (NAFLD) are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7 and/or NaV1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7 and/or NaV1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7 and/or Nav1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: Disclosed are compositions of matter having an amino acid sequence of SEQ ID NO:4, or a pharmaceutically acceptable salt thereof, including embodiments comprising a toxin peptide analog related to ShK, HmK, and AETX-K and pharmaceutical compositions or medicaments containing them along with a pharmaceutically acceptable carrier. Some embodiments include a half-life extending moiety. Also disclosed are a method of preventing or mitigating a relapse of a symptom of multiple sclerosis and a method of treating an autoimmune disorder using the compositions.