Abstract: The present invention provides, among other things, methods of formulating nucleic acid-containing nanoparticles with an enzyme to afford efficient delivery of payload to a cell or tissue of interest via subcutaneous administration. In some embodiments, the present invention provides a process in which mRNA-loaded lipid nanoparticles are co-mixed with various amounts of hyaluronidase and administered via subcutaneous administration. The resulting payload can be efficiently delivered to the liver and other organs or tissues of a treated subject.

Abstract: Provided herein are oligonucleotides for inhibiting the expression of Double Homeobox 4 (DUX4) and methods of using the oligonucleotides for reducing DUX4 expression in a subject.

Abstract: Compositions and methods for editing, e.g., introducing double-stranded breaks, within the KLKB1 gene are provided. Compositions and methods for treating subjects having hereditary angioedema (HAE), are provided.

Abstract: The present disclosure relates to a polymer-coated gold nanoparticle-aptamer nanoconstruct having reactive oxygen species sensitivity and capable of treating inflammatory diseases through reactive oxygen species scavenge and TNF-? capture.

Abstract: The present disclosure relates to recombinant vectors expressing the human ND4 gene, methods of preparing recombinant vectors expressing the human ND4 gene, and uses thereof. Recombinant AAV2 vectors as disclosed herein are useful in treating Leber Hereditary Optic Neuroretinopathy (LHON), including ND4-related LHON.

Abstract: The present disclosure provides an isolated immune cell which expresses a receptor, interleukin-7, and chemokine (C—C motif) ligand 19.

Abstract: An agent for inhibiting the action of a target RNA based on RNA interference and antisense oligonucleotide (ASO). The RNA interference agent includes a passenger strand and a guide strand for a target RNA. Both ends of double-stranded RNA formed pairing of the passenger and guide strands are blunt ends, and one or two or more of the units represented by formula (1) and formula (2) below are provided at the following positions (a) and (b): (a) 5? end side and 3? end side of the passenger strand, (b) 3? end side of the guide strand where X represents an oxygen atom or sulfur atom, where X represents an oxygen atom or sulfur atom.

Abstract: Among other things, the present disclosure provides oligonucleotides, compositions, and methods for preventing and/or treating various conditions, disorders or diseases. In some embodiments, provided technologies comprise nucleobase modifications, sugar modifications, internucleotidic linkage modifications and/or patterns thereof, and have improved properties, activities and/or selectivities. In some embodiments, provided technologies target MAPT. In some embodiments, the present disclosure provides MAPT oligonucleotides, compositions and methods for preventing and/or treating MAPT-associated conditions, disorders or diseases, such as Alzheimer's Disease (AD) or Frontotemporal Dementia (FTD).

Abstract: Provided herein are compositions and methods for the multiplexed profiling of RNA and DNA modifications across transcriptomes and genomes, respectively. The methods combine molecular recognition of non-canonical features (e.g., base modifications, backbone modifications, lesions, and/or structural elements) of a target nucleic acid with a step of writing the information from this recognition event into the neighboring genetic sequence of the target nucleic acid using a barcode. The resultant barcoded nucleic acids are then converted into sequencing libraries and read by DNA/RNA sequencing methods. This step reveals the sequence of the barcode, which is correlated with the non-canonical feature in the target nucleic acid(s). The high throughput profiling methods described herein allow for identification and/or localization of one or more modifications in a target nucleic acid. The methods also allow for identification of the nature and location of several or all DNA/RNA modifications in parallel.

Abstract: Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic ?-Gal A protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of Fabry disease.

Abstract: The present invention relates to nucleic acids for inhibiting expression of a target gene in a cell, comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene to be inhibited. The first strand of the nucleic acid has a terminal 5? (E)-vinylphosphonate nucleotide that is linked to the second nucleotide in the first strand by a phosphodiester linkage.

Abstract: Compositions and methods relating to regulation of gene expression are described. In some embodiments, the present disclosure provides compositions and methods for the regulation of gene expression using nucleic acid constructs. In some embodiments, the present disclosure recognizes the utility of alternative splicing in regulation of gene expression in a nucleic acid construct. In some embodiments, the present disclosure recognizes the utility of regulating gene expression utilizing ligand-binding aptamers.

Abstract: Described herein are aptamers that bind to the transferrin receptor (e.g., CD71) and can be used, in part, for depleting transferrin receptor-expressing cells from a population of therapeutic cells. These aptamer compositions can be used in methods for isolating and/or enriching cells expressing CD71 or depleting cell populations of cells expressing CD71, including for example, tumor cells. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Abstract: The disclosure relates, in some aspects, to methods and compositions for production of immunomodulatory compositions. In some embodiments, the disclosure provides host cells which have been treated ex vivo with one or more oligonucleotide agents capable of controlling and/or reducing the differentiation of the host cell. In some embodiments, compositions and methods described by the disclosure are useful as immunogenic modulators for treating cancer.

Abstract: Provided herein is a method of treating low turnover renal osteodystrophy in a subject being administered an agent that reduces bone turnover comprising measuring a level of one or more miRNAs in a sample from the subject. The miRNA being measured can include miRNA-30b, miRNA-30c, miRNA-125b and miRNA-155. Administration of the agent that reduces bone turnover can be stopped if the level of the one or more miRNAs measured is lower than a level of the one or more miRNAs measured in a control subject. Administration of the agent that reduces bone turnover can be continued if the level of the one or more miRNAs measured is not lower than a level of the one or more miRNAs measured in a control subject.

Abstract: Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in genes can modulate the expression level of functional proteins in patients and/or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency and/or mitochondrial function deficit.

Abstract: The present invention provides constructs comprising modified riboswitches to regulate expression of a transgene within a subject. Methods of treating a disease, specifically an eye disease, are also contemplated.

Abstract: The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a) (Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.

Abstract: An engineered DNA molecule capable of being replicated in a cell, comprising a poly (A) tail coding sequence that makes the engineered DNA molecule more conservative when replicated in cells, particularly in prokaryotic cells, while adjusting the expression level of RNA in eukaryotic cells. Also provided are an RNA comprising the poly (A) tail and a use thereof.

Abstract: The present subject matter provides compositions. formulations and methods for preventing or reducing proliferation or migration of retinal cells or epithelial to mesenchymal transition in ocular cells or cells from other tissues.