Abstract: Synthetic ?v?6 integrin ligands of Formula I having serum stability and affinity for integrin ?v?6, which is a receptor expressed in a variety of cell types, are described. The described ligands are useful for delivering cargo molecules, such as RNAi agents or other oligonucleotide-based compounds, to cells that express integrin ?v?6, and thereby facilitating the uptake of the cargo molecules into these cells. Compositions that include ?v?6 integrin ligands and methods of use are also described.

Abstract: Disclosed herein are engineered oligonucleotides for selective inhibition of polypeptide expression and activity. Also disclosed herein are methods of selectively inhibiting polypeptide expression and activity contacting an engineered oligonucleotide with a polynucleotide encoding the polypeptide.

Abstract: Among other things, the present disclosure provides technologies for altering splicing, particularly for increasing inclusion of exons in splicing products. In some embodiments, the present disclosure provides SMN2 oligonucleotides, compositions, and methods thereof. In some embodiments, the present disclosure provides chirally controlled SMN2 oligonucleotide compositions. In some embodiments, provided oligonucleotides and compositions can increase level of an exon 7-containing SMN2 splicing product and/or a gene product thereof. In some embodiments, the present disclosure provides methods for treatment of splicing-related conditions, disorders and diseases. In some embodiments, the present disclosure provides methods for treating SMN2-related conditions, disorders and diseases such as SMA (spinal muscular atrophy) and ALS (amyotrophic lateral sclerosis).

Abstract: Developed and provided is: a nucleic acid agent that is efficiently delivered to the central nervous system, to which drug delivery is inhibited by the blood brain barrier mechanism, and that provides an antisense effect to a target transcription product at the delivery site; and a composition containing such a nucleic acid agent. Provided is a double-stranded nucleic acid complex consisting of a first nucleic acid strand and a second nucleic acid strand that are annealed to each other; wherein the first nucleic acid strand hybridizes with part of a target transcription product and has an antisense effect on the target transcription product; and wherein the second nucleic acid strand includes a base sequence complementary to the first nucleic acid strand and is conjugated to a phosphatidylethanolamine or an analog thereof.

Abstract: The present invention relates a formulation and capsule suitable for oral administration. The invention further relates to the use of the formulation and capsule for treating inflammatory bowel diseases, for instance ulcerative colitis (UC) or Crohn's disease.

Abstract: The application relates to methods for compositions for identifying lncRNA loci associated with target genotypes or phenotypes, including desirable plant genotypes or phenotype. The application also relates to regulatory regions and genes associated with drug resistance, such as resistance to BRAF-inhibitors. Such regulatory regions and genes form the basis for methods for identifying resistance to BRAF-inhibitors, which is useful for improving disease prognosis, treatment, and likely outcomes. The regulatory regions and genes are also suitable targets for therapy in melanoma that is resistant to BRAF-inhibitors.

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

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

Abstract: The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Abstract: Disclosed herein are methods for inhibiting or activating the transcription of a gene of interest, or inhibiting or activating the transcription of specific mRNA isoforms of a gene by using antisense oligonucleotides and/or small molecules. Also described herein are methods for activating transcription from a promoter and increasing overall gene expression by creating of a new splice site in a gene of a cell.

Abstract: Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a ?-catenin inhibitor and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a ?-catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a ?-catenin inhibitor, such as a ?-catenin nucleic acid inhibitor molecule.

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure.

Abstract: The invention relates to the field of RNA stabilisation, and more particularly to the use of deuterium oxide (D2O) during storage and/or synthesis of RNA molecules. Described herein are deuterium-stabilised ribonucleic acid (RNA) molecules that display an increased resistance to thermal and enzymatic hydrolysis. Also described are aqueous compositions comprising stabilized RNA molecules and methods for making same. The invention is particularly useful for in the manufacture of RNA-based therapeutics, such as mRNA vaccines, to render them less sensitive to temperature fluctuations.

Abstract: Compositions and methods for treating cancer in a subject in need thereof are described that includes administering a therapeutically effective amount of an oligonucleotide that inhibits the binding of splicing regulator SRSF1 or SRSF2 to MDM2 exon 4 or 11.

Abstract: The invention relates to a saRNAs useful in upregulating the expression of the SIRT1 gene and therapeutic compositions comprising the saRNA. Methods of using the saRNA and the therapeutic compositions are also provided.

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

Abstract: A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.

Abstract: The invention provides a single-stranded oligonucleotide represented by the formula [Xz-Lx]m-X-Y-[Ly-Yz]n, wherein X is represented by Xa-Xb, Xa is coupled with Y, and Xb and Y hybridize. Xa is composed of 1 to 40 nucleotides and contains at least one modified-nucleotide. Xb is composed of 4 to 40 nucleotides and contains at least one modified-nucleotide. Y is composed of 4 to 40 nucleotides and contains at least one ribonucleotide. Xz and Yz are composed of 5 to 40 nucleotides and contain at least one modified-nucleotide. Nucleotide sequences X, Xz and Yz have an antisense sequence capable of hybridizing with a target RNA. Lx and Ly are composed of 0 to 20 nucleotides.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN1 RNA in a cell or subject, and in certain instances reducing the amount of ATXN1 in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include gait and limb ataxia, cognitive impairments, difficulty with speaking and swallowing, atrophy of the cerebellum and brainstem in magnetic resonance imaging (MRI), neurochemical abnormalities in the cerebellum and brainstem detected via magnetic resonance spectroscopy (MRS), and death within 10-15 years of symptom onset. Such neurodegenerative diseases include Spinocerebellar ataxia type 1.

Abstract: Described herein are aptamers capable of binding to growth differentiation factor 11 (GDF11) protein; compositions comprising a GDF11 binding aptamer with a GDF11 protein; and methods of making and using the same.