Abstract: This invention provides nanoparticles containing protein-polynucleotide complexes and methods of manufacture and methods of their use. These particles, when administered to a subject in need, are capable of delivering these complexes to target cells and target intracellular locations where they can perform a therapeutic function. In some embodiments, this therapeutic function includes gene editing, induction of gene skipping, and regulation of gene expression. The instant nanoparticles are generally formed by designing and synthesizing the polynucleotide to according to its intended function, combining it with a protein selected for its substrate specificity and enzymatic function in a manner to form a polynucleotide-protein complex, encapsulating the complexes by dispersion into a water-insoluble surfactant system, optionally adding a targeting ligand, and stabilizing the nanoparticles by crystallization of the ligand to the surface of the nanoparticles.

Abstract: The present invention provides novel, stable lipid particles having a non-lamellar structure and comprising one or more active agents or therapeutic agents, methods of making such lipid particles, and methods of delivering and/or administering such lipid particles. More particularly, the present invention provides stable nucleic acid-lipid particles (SNALP) that have a non-lamellar structure and that comprise a nucleic acid (such as one or more interfering RNA), methods of making the SNALP, and methods of delivering and/or administering the SNALP.

Abstract: In certain embodiments, the present disclosure provides compounds and methods of increasing the amount or activity of a target protein in a cell. In certain embodiments, the compounds comprise a translation suppression element inhibitor. In certain embodiments, the translation suppression element inhibitor is a uORF inhibitor. In certain embodiments, the uORF inhibitor is an antisense compound.

Abstract: Provided herein are compositions for gene modification or editing and methods of using same to treat or prevent certain conditions. Specific compositions and methods capable of safely and effectively editing gene targets expressed in the liver to durably lower LDL-C thereby treating a leading cause of cardiovascular disease are disclosed.

Abstract: Disclosed herein are compositions, kits, and methods for treating a disorder of genomic imprinting in a subject. The method may include modifying a zinc-finger protein 274 (ZNF274) binding site on maternal chromosome 15 at position 15q11-q13 of the subject, such that the binding of a ZNF274 protein to the ZNF274 binding site is reduced relative to a control. The ZNF274 binding site comprises a polynucleotide having at least 90% sequence identify to SEQ ID NO: 1 or SEQ ID NO: 42. Further provided are DNA targeting systems that bind to a ZNF274 binding site or to a gene encoding a ZNF274 protein.

Abstract: This application relates to recombinant adeno-associated virus (rAAV) packaging and/or producer cell lines which have been engineered to reduce expression and/or activity of one or more genes and/or proteins to increase rAAV titers. The methods of generating the engineered cell lines have also been described herein.

Abstract: Provided are immunostimulatory bacteria and oncolytic viruses, and pharmaceutical compositions containing the bacteria and/or viruses, that act as three prime repair exonuclease 1 (TREX1) antagonists. The bacteria and viruses are for treating tumors that are human papillomavirus (HPV) positive or that have a high tumor mutational burden (TMB). The immunostimulatory bacteria and oncolytic viruses encode therapeutic products such RNAi, such as shRNA and microRNA, that mediate gene disruption and/or inhibit expression of TREX1, or that inhibit TREX1. The bacteria contain additional modifications to enhance their anti-tumor activity. The bacteria and viruses are used for treatment of tumors in which TREX1 expression correlates with the presence of the tumor or properties of the tumor, such that inhibition of TREX1 advantageously treats the tumor.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy. Also provided are kits for detecting the amount of SMN protein in a sample of cerebrospinal fluid.

Abstract: This disclosure provides systems, methods, and compositions for RNA-guided RNA-targeting CRISPR effectors for the treatment of diseases as well as diagnostics. In some embodiments, nucleotide deaminase functionalized CRISPR systems for RNA editing RNA knockdown, viral resistance, splicing modulation, RNA tracking, translation modulation, and epi-transcriptomic modifications are disclosed.

Abstract: Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a disease which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Abstract: Described herein are compositions and methods for the production and quantification of barcoded or unique molecular identifier (UMI)-labeled substrates. In one aspect, the substrate is a bead comprising a template oligonucleotide that is elongated by successive extension reactions to provide a bead with an oligonucleotide comprising a plurality of barcodes and conserved anchor regions. Methods are also described for quantifying the amount of template oligonucleotide loaded onto the substrate and the products of the extension reaction after each round and after the final extension.

Abstract: Vectors having a nucleotide sequence having SEQ ID NO:1 or a nucleotide sequence having at least 85% identity to SEQ ID NO:1, or a portion thereof, that is capable of regulating bocaparvovirus replication, or vectors having the complement of the nucleotide sequence, and methods of using the vectors, are provided.

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Huntingtin (HTT) gene, as well as methods of inhibiting expression of an HTT gene and methods of treating subjects having an HTT-associated disease or disorder, e.g., Huntington's disease, using such dsRNAi agents and compositions.

Abstract: Described are methods for enhancing exon skipping in a pre-mRNA of interest, comprising contacting the pre-mRNA with interfering oligonucleotides such as antisense, siRNA, and miRNA. The exon skipping methods are associated with methods of treating a variety of diseases and conditions, including cancer.

Abstract: This disclosure relates to the use of miRNA-483 and its target genes, UBE2C, pVHL and HIF1alpha, in managing the treatment of cardiovascular and inflammatory diseases. In certain embodiments, this disclosure relates to pharmaceutical compositions comprising a miR-483 mimic and/or an HIF inhibitor and a pharmaceutically acceptable excipient for use in treating or preventing a vascular disease or condition. In certain embodiments, the miR-483 mimic is a double stranded nucleobase polymer or an expression vector that expresses mature human miR-483-5p and miR-483-3p sequences or operable fragments and variants.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: This invention relates to methods and materials for multiplexed utilization of collections of functional ligands, particularly to methods and materials for selecting for and/or utilizing particular desirable traits of functional ligands in a multiplexed manner, and more particularly to methods and materials for selecting for and/or utilizing particular structural changes of functional ligands in a multiplexed manner.

Abstract: The subject invention pertains to composition and methods of using said composition as an in vitro biosensor of small molecules in biological and/or environmental samples using enzyme-assisted nucleic acid reactions. The methods and compositions can be used to sense and/or transduce the signal of a sensing event mediated by allosteric proteins, endonucleases and nucleic acid reactions. This invention allows the rapid development and setup of one-pot assays to provide results in minutes. The methods and compositions may be used to generate an electrochemical, fluorescent, colorimetric, and/or luminescent output and the methods can be performed in different modalities, including a solution-based or paper-based assay.

Abstract: The invention relates to saRNA targeting an HNF4a transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.

Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the complement factor B (CFB) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a CFB gene and to methods of treating or preventing a CFB-associated disease in a subject.