Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

Abstract: The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating cystic fibrosis, e.g., in subjects having a mutation resulting in F508del, are described.

Abstract: Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy.

Abstract: Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject who is administered the one or more compositions. The target biomolecule is a precursor protein such as a precursor protein of CLTA4.

Abstract: Among the various aspects herein is the provision of compositions and methods for modulating MYCT1. Methods are provided for regulating tumor angiogenesis (anti-angiogenesis, Myct1-targeted vascular control) and/or immunostimulation, which inhibit tumor growth, in a subject. Methods are provided to quantify MYCT1 to predict responsiveness of a subject having a cancer or tumor to a treatment, guide treatment decisions, select subjects for clinical trials, and evaluate the clinical efficacy of certain therapeutic interventions.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the complement component C3 gene (C3). The invention also relates to methods of using such RNAi agents to inhibit expression of a C3 gene and to methods of preventing and treating a C3-associated disorder, e.g., cold agglutinin disease (CAD), warm autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH), lupis nephritis (LN), bullous pemphigoid, pemphigus, e.g., pemphigus vulgaris (PV) and pemphigus foliaceus (PF), and C3 glomerulopathy.

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relate to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

Abstract: The present disclosure relates to compositions, such as siRNA molecules and FN3 domains conjugated to the same, as well as methods of making and using the molecules.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: A lipid-binding drug for binding to a membrane-based or membrane lipid comprises at least one aptamer having a sequence selected from the group consisting of GGCGGCAAAAAAAAAA (SEQ ID NO: 1), GGCGGCAAAAAAAAAAA (SEQ ID NO: 2), GGCGGCAAAAAAAAAAAA (SEQ ID NO: 3), GGCGGCAAAAAAAAAAAAA (SEQ ID NO: 4), GGCGGCGGGGGGGGGG (SEQ ID NO: 5), GGCGGCGGGGGGGGGGG (SEQ ID NO: 6), GGCGGCGGGGGGGGGGG (SEQ ID NO: 7), GGCGGCGGGGGGGGGGG (SEQ ID NO: 8), CAAAAGGAGCAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 9) CAAAAGGAGCAAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 10), CAAAAGGAGCAAAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 11), CAAAAGGAGCAAAAAAAAAAAAAAAAAAAAAAAAAA (SEQ ID NO: 12), CAAAAGGAGCGGGGGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 13), CAAAAGGAGCGGGGGGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 14), CAAAAGGAGCGGGGGGGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 15), and CAAAAGGAGCGGGGGGGGGGGGGGGGGGGGGGGGGG (SEQ ID NO: 16).

Abstract: The present invention relates, in general to, compounds, compositions and methods useful for modulating gene expression of multiple target nucleic acids by a single chemical entity.

Abstract: Embodiments of the disclosure concern the use of expression constructs in which at least one polyA signal is embedded upstream of an expressible transcript, such as within a 5? UTR for the transcript, for example. In certain embodiments, the polyA signal is comprised within a ligand-binding aptamer, and the binding of the ligand to the aptamer, or lack thereof, dictates the outcome for the expressible transcript. In specific embodiments, absence of the ligand causes the expressed transcript having a polyA in its 5? UTR to be expressed but then degraded, whereas presence of the ligand causes inhibition of degradation upon expression of the expressible transcript. More than one ligand-binding aptamer may be present on the same expression construct.

Abstract: Provided are antisense oligomers targeted against bacterial mRNAs and other macromolecules associated with a biochemical pathway and/or cellular process, and related compositions and methods of using the oligomers and compositions to treat an infected mammalian subject, for example, as primary antimicrobials or as adjunctive therapies with classic antimicrobials.

Abstract: The present invention is directed to a storage-stable formulation of long-chain RNA. In particular, the invention concerns a dry powder composition comprising a long-chain RNA molecule. The present invention is furthermore directed to methods for preparing a dry powder composition comprising a long-chain RNA molecule by spray-drying. The invention further concerns the use of such a dry powder composition comprising a long-chain RNA molecule in the preparation of pharmaceutical compositions and vaccines, to a method of treating or preventing a disorder or a disease, to first and second medical uses of such a dry powder composition comprising a long-chain RNA molecule and to kits, particularly to kits of parts, comprising such a dry powder composition comprising a long-chain RNA molecule.

Abstract: The present disclosure is related to an engineered nucleic acid encoding a post-poly A signal RNA 3? to a terminator for expression of protein, and/or non-coding RNA. Also provided herein are methods for reducing epigenetic silencing, genetic modification, transcriptional regulation of the engineered nucleic acid described herein.

Abstract: A nanoparticle includes an icosahedral-shaped plant virus particle; an RNAi construct; and one or more endolysosomal release agents, wherein the RNAi construct is noncovalently loaded within the icosahedral-shaped plant virus particle.

Abstract: Provided herein are compounds and methods for gene silencing. The compound includes a RNA directly conjugated to an albumin-binding group. The method includes administering a compound comprising a RNA directly conjugated to an albumin-binding group to a subject in need thereof.

Abstract: In an embodiment, a strand displacement system including a DNA/PNA complex, an input DNA strand, where the DNA/PNA complex binds to the input DNA strand forming a complex and displaces a PNA intermediate and forms an activated domain on the PNA, and a Bi complex that reacts with the activated domain on the PNA to thereby release an output DNA strand. In an additional embodiment, a fluorogenic sensor including a heteroduplex between an achiral PNA strand and a fluorogenic aptamer, where the fluorogenic aptamer includes L-RNA, an input DNA strand, where the input DNA strand binds to the heteroduplex and displaces an incumbent fluorogenic aptamer strand and forms an activated domain on that strand, and a dye.

Abstract: The present invention relates to oligonucleotides which up-regulate or restore the expression of progranulin in cells, and their use in the treatment of neurological disorders, and disorders associated with progranulin haploinsufficiency.

Abstract: The present invention is directed to the field of RNA formulation, in particular to lyophilization of RNA. The invention provides a method for lyophilization of RNA. The present invention further concerns a lyophilized composition obtainable by the inventive method, a pharmaceutical composition, a vaccine and a kit or kit of parts. Moreover, the present invention provides a novel use of a lyoprotectant for lyophilizing RNA, the use of the inventive method in the manufacture of a medicament as well as the first and second medical use of the composition obtainable by the inventive method, the pharmaceutical composition, the vaccine or the kit or kit of parts according to the invention.