The present disclosure features useful compositions and methods to treat nucleotide repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MSH3 activity.

Provided is a DNA aptamer specifically binding to an insulin receptor, a pharmaceutical composition for treating diabetes including the same, and a composition for diagnosing diabetes including the DNA aptamer.

The insulin receptor aptamer may be effectively used in compositions for preventing or treating insulin-related diseases due to better downstream signaling activity of the insulin receptor than insulin or existing insulin receptor aptamers conventionally used for treatment of insulin-related diseases such as diabetes.

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.

One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The sense strand of the dsRNA agent comprises at least one thermally destabilizing nucleotide, and at least one said thermally destabilizing nucleotide occurring at a site opposite to the seed region (positions 2-8) of the antisense strand; and the antisense strand of the dsRNA agent comprises at least two modified nucleotides that provide the nucleotide a steric bulk that is less than or equal to the steric bulk of a 2′-OMe modification, wherein said modified nucleotides are separated by 11 nucleotides in length. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA agents suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA agents, e.g., for the treatment of various disease conditions.

The disclosure includes antisense oligonucleotides, including gapmer antisense oligonucleotides, along with methods of making and use, e.g., against HBV.

The present disclosure provides modified short-interfering ribosomal nucleic acid compositions that have one or more uracil bases replaced a 5-fluorouracil molecule. More specifically, the present disclosure reveals that the replacement of uracil nucleotides within an siRNA nucleotide sequence with a 5-fluorouracil increases the ability of the short interfering RNA to inhibit cancer progression and tumorigenesis when compared to known cancer therapeutics. As such, the present disclosure provides various short-interfering nucleic acid compositions having 5-fluorouracil molecules incorporated in their nucleic acid sequences and methods for using the same. The present disclosure further provides pharmaceutical compositions comprising the modified nucleic acid compositions, and methods for treating cancers using the same.

Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the programmed cell death 1 ligand 1 (PD-L1) gene, and methods of using such RNAi agents to inhibit expression of a PD-L1 gene and methods of treating subjects having a PD-L1-associated disorder.

Provided herein are bispecific personalized aptamers that induce the cell death of cancer cells and methods of use thereof.