Abstract: The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with target gene expression or inhibit target gene expression and therapeutic uses of such products.

Abstract: The present disclosure provides methods of treating subjects having inflammation with an Angiopoietin-Like 7 (ANGPTL7) inhibitor and a glucocorticoid, methods of decreasing glucocorticoid-induced ophthalmic conditions in subjects, and methods of identifying subjects having an increased risk of developing glucocorticoid-induced ophthalmic conditions.

Abstract: The present invention provides compositions having one or more agents capable of increasing expression of one or more endogenous tumor suppressive mi RNAs in one or more producing cells, such that the endogenous mi RNAs can affect one or more target cancer cells. Further provided are method and uses thereof for treating cancer.

Abstract: Provided herein are, inter alia, nucleic acid conjugates including a non-cell penetrating ribonucleic acid compound attached at its 3? end to a phosphorothioate polymer. Attachment of the phosphorothioate polymer to the non-cell penetrating ribonucleic acid conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating ribonucleic acid. The nucleic acid conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer, inflammatory disease, and pain.

Abstract: This current invention provides methods and agents for preventing and treating autoimmune and lymphoproliferative disease by targeting pathogenic age-associated B cells as well as methods of detecting these pathogenic age-associated B cells as a method of diagnosing and predicting autoimmune disease and other lymphoproliferative and chronic inflammatory disorders. The current invention also provides targets for drug development and basic research for autoimmune diseases and other lymphoproliferative and chronic inflammatory disorders.

Abstract: The present disclosure provides miRNA mimics targeting CDK4 and/or CDK6, and compositions comprising the same. Methods for the treatment of tumors, including but not limited to colon cancer, comprising administering a modified oligonucleotide comprising a miRNA are also disclosed herein.

Abstract: Disclosed are genetic methods and tools for colon cancer disease classification in disease subtypes, CMS1, CMS2, CMS3, CMS4, as well as improved methods for rapid, more accurate, and more reliably reproducible disease subtype determination. Tailored treatment protocols are also provided, employing the predicted CMS of the subject sample. Genetic sequence binding targets for some or all of these gene panels may be affixed to a solid substrate, and included as part of a screening tool and/or diagnostic kit. The expression levels of the genes may be assessed to provide a genetic signature for a subtype or lack of subtype (CMS1, CMS2, CMS3, CMS4, combination subtype). The methods employ a scoring system, wherein a score is derived from the genetic expression profile/signature of the panel of selected genes, and a qualifying continuous score for each CMS subtype is determined against a predictive threshold for each colon cancer subtype.

Abstract: Genome editing systems, guide RNAs, and CRISPR-mediated methods are provided for altering portions of the HBG1 and HBG2 loci, portions of the erythroid specific enhancer of the BCL11A gene, or a combination thereof, in cells and increasing expression of fetal hemoglobin.

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: Disclosed herein are compositions and methods for inducing, promoting, or enhancing an immune response in a subject. For example, the disclosed compositions and methods can be used prophylactically to prevent viral/microbial infections or therapeutically to treat acute infections. In some embodiments, the disclosed method involves administering to the subject a composition comprising in vitro transcribed (IVT) RNA comprising short interspersed nuclear elements (SINEs), such as Alu repeats. In some embodiments, the disclosed compositions and methods can be used to induce, promote, or enhance any immune response in a subject, including an anti-viral, anti-microbial, anti-fungal, or anti-parasite response. In some embodiments, the disclosed compositions can be administered to any mucosal barrier, such as lungs or intestines, e.g. to enhance an innate immune response against a virus or pathogen.

Abstract: The present disclosure provides methods of treating patients having an ophthalmic condition, methods of identifying subjects having an increased risk of developing an ophthalmic condition, methods of detecting human angiopoietin like 7 (ANGPTL7) variant nucleic acid molecules and variant polypeptides, and ANGPTL7 variant nucleic acid molecules and variant polypeptides.

Abstract: Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamer comprises one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.

Abstract: The invention is a method for treating a heart disease, in particular acute myocardial infarction (AMI) in a subject comprising the step of administering to the subject a Tjp1 inhibitor, wherein administration of said Tjp1 inhibitor promotes cardiomyocyte proliferation. The invention further includes use of Tjp1 inhibitor in the manufacture of a medicament for a heart disease, a patch, and a nucleic acid encoding a Tjp1 inhibitor. In a particular embodiment, the Tjp1 inhibitor is a nucleic acid, i.e. an siRNA or shRNA of Tjp1. The invention also includes administration of said Tjp1 inhibitor in combination with Neuregulin-1 (NRG1), Fibroblast growth factor (FGF), Vascular endothelial growth factor (VEGF) or Follistatin-like 1 (Fst1) and wherein said inhibitor is delivered in an adeno-associated virus of serotype 9 (AAV 9).

Abstract: The present invention provides novel compounds that target thrombocyte activity or aggregation capacity through cellular components for the treatment of diseases associated with Non-Alcoholic Fatty Liver Disease (NAFLD). The invention provides these compounds for treating non-alcoholic steatohepatitis (NASH), a progressed stage of NAFL (non-alcoholic fatty liver), in order to avoid the development of liver cirrhosis and Hepatocellular Carcinoma (HCC). Further provided are pharmaceutical compositions, comprising the compounds of the invention, and methods for screening new NASH therapeuticals.

Abstract: Methods are disclosed herein for treating glaucoma in a subject. In some embodiments, the methods increase retinal ganglion cell survival. The disclosed methods use exosomes and/or miRNA.

Abstract: The present invention relates to photoactivatable compounds and methods of use thereof for determining binding site and other structural information about RNA transcripts. The invention also provides methods of identifying RNA transcripts that bind compounds and are thus druggable, methods of screening drug candidates, and methods of determining drug binding sites and/or accessible or reactive sites on a target RNA.

Abstract: The present disclosure relates to antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase. AONs of the present disclosure may be useful in treating diseases associated with the modulation of the expression of the enzyme glycogen synthase, such as Pompe disease. Also provided by the present disclosure are compositions comprising AONs, as well as methods of down regulating mRNA coding for glycogen synthase, methods for reducing glycogen synthase in skeletal and cardiac muscle, and methods for treating Pompe disease.

Abstract: The present invention provides novel, serum-stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles. More particularly, the present invention provides serum-stable nucleic acid-lipid particles (SNALP) comprising a nucleic acid (e.g., one or more interfering RNA molecules), methods of making the SNALP, and methods of delivering and/or administering the SNALP (e.g., for the treatment of cancer). In particular embodiments, the present invention provides tumor-directed lipid particles that preferentially target solid tumors. The tumor-directed formulations of the present invention are capable of preferentially delivering a payload such as a nucleic acid to cells of solid tumors compared to non-cancerous cells.

Abstract: This invention provides a kit or a device for the detection of pancreatic cancer, comprising a nucleic acid(s) capable of specifically binding to a miRNA(s) in a sample from a subject, and a method for detecting pancreatic cancer, comprising measuring the miRNA(s) in vitro.

Abstract: The invention provides novel and versatile classes of riboregulators, including inter alia activating and repressing riboregulators, switches, and trigger and sink RNA, and methods of their use for detecting RNAs in a sample such as a well and in modulating protein synthesis and expression.