Abstract: The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with excess growth hormone using antisense compounds or oligonucleotides targeted to growth hormone receptor (GHR).

Abstract: The present disclosure relates to isolated compounds including a nucleic acid sequence capable of hybridizing to an RNA sequence 10 to 270 nucleobases downstream of the transcription start site of a mammalian microRNA-379 transcript; method of treating diabetic nephropathy in a subject with the compounds; and method of inhibiting expression of a mammalian microRNA-379 megacluster with the compounds.

Abstract: The present invention provides a pharmaceutical agent which causes skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene with a high efficiency. The present invention provides an oligomer which efficiently enables to cause skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PNPLA3 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PNPLA3.

Abstract: Provided are non-small cell lung cancer markers and the use thereof in diagnosing and monitoring diseases in vitro. The non-small cell lung cancer markers include at least one of 26 selected detectable mature microRNAs existing stably in human serum or plasma. Also provided are probe combinations, a kit and a biochip for detecting the non-small cell lung cancer markers. The invention further provides a method for detecting the said lung cancer markers. The method in the present invention enables extensive detection spectrum, high sensitivity, low cost, convenient sample taking and preservation. The method can be applied in the general survey of disease, solves problems of low specificity and sensitivity encountered with previous single markers, and increases significantly the clinical detection rate of diseases. The methods provide an effective means for diagnosing diseases at an early stage.

Abstract: Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for AAT.

Abstract: The present application relates to the field of cancer, particularly that of cancers with high MDM4 protein levels (such as melanoma, breast, colon or lung cancers, glioblastoma, retinoblastoma, etc.). It is shown herein that direct and selective inhibition of MDM4, e.g., by antisense RNA, leads to growth inhibition of cancer cells and sensitization to chemo or targeted therapies. Also provided are simple ways of determining which patients are most amenable for such treatment by comparing specific transcript levels.

Abstract: A pharmaceutical composition comprising a peptide-polynucleotide complex, and methods of use thereof.

Abstract: The present disclosure provides nucleic acid molecules encoding an engineered antigen receptor, such as a chimeric antigen receptor or exogenous T cell receptor, and an inhibitory nucleic acid molecule, such as an RNA interference molecule. The present disclosure further relates to nucleic acids, DNA constructs, vectors, pharmaceutical compositions, genetically-modified cells, and methods of treatment that utilize the nucleic acid molecules of the invention.

Abstract: The disclosure relates to nucleic acids that contain modifications at the 5?-end, 3?-end or 5?-end and 3?-ends, and compounds that can be used to make the modified nucleic acids are disclosed. The modified nucleic acids have improved expression, lower immunogenicity and improved stability compared to unmodified nucleic acids.

Abstract: RNA interference (RNAi) agents and RNAi agent conjugates for inhibiting the expression of the LPA (apo(a)) gene are described. Pharmaceutical compositions comprising one or more LPA RNAi agents optionally with one or more additional therapeutics are also described. Delivery of the described LPA RNAi agents to liver cells in vivo provides for inhibition of LPA gene expression and treatment of cardiovascular and cardiovascular-related diseases.

Abstract: Provided are methods and compositions for identifying a miRNA profile for a particular condition, such as pancreatic disease, and using the profile in assessing the condition of a patient.

Abstract: The present invention relates to the design and development of recombinant protein for the delivery of silencer RNA complex to mediate RNA interference since it represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes across the blood-brain barrier (BBB). To overcome challenges due to this barrier for biologics and other biological complex, the present invention describes a method wherein peptide having sequence GGGGHLNILSTLWKYRC represented by SEQ ID NO. 1 known to target specific gangliosides was linked to a double-stranded RNA binding protein to bind and deliver silencer RNA to the brain parenchyma. The designed fusion protein comprising a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) and a brain targeting peptide sequence that binds GM1. Conformation-specific binding of TARBP2 domain to silencer RNA results in the formation of homogenous serum-stable complex with GM1 targeting potential.

Abstract: Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

Abstract: The invention provides a method of treating preeclampsia, fetal growth restriction (FGR or IUGR), obesity in pregnancy, post-partum cardiomyopathy (heart failure in mothers), cancer and diabetic retinopathy, cardiomyopathy, myocardial infarction, wet microdegeneration and other disorders where angiogenesis is aberrant either diminished or exacerbated, comprising modulating the activity of micro RNA (miRNA). Also provided are an MiRNA modulator or a combination thereof or functional fragments or homologues thereof for use in the treatment of preeclampsia, fetal growth restriction, obesity in pregnancy, cancer, and diabetic retinopathy, cardiomyocyte infarction, wet microdegeneration as well as other disorder where angiogenesis is aberrant either diminished or exacerbated. Methods of modulating angiogenesis and pharmaceutical compositions using miR-122, miR-374b or inhibitors of miR-152 or miR195 are also provided together with methods of diagnosis using the miRNAs.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Lipid transport and metabolism gene, in particular, by targeting natural antisense polynucleotides of a Lipid transport and metabolism gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of a Lipid transport and metabolism genes.

Abstract: The present invention is directed to a method of treating cancer using interfering RNA duplexes to mediate gene silencing. The present invention is also directed to interfering RNA duplexes and vectors encoding such interfering RNA duplexes.

Abstract: Methods for inhibiting oligonucleotide activity in vitro or in vivo to a cell that are formulated with at least one oligonucleotide encapsulated in a lipid nanoparticle are disclosed.

Abstract: Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

Abstract: The disclosure teaches antagonists of Hepatitis C Virus (HCV) derived microRNA, which are useful in methods for treating and protecting against HCV-mediated hepatocellular carcinogenesis.