Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or N patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.

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.

Disclosed is a method of treating a subject who has a neurological disease. In one aspect, the method includes a step of administering an effective dose of a SYF2 antisense or inhibitory nucleic acid to a subject in need thereof, thereby restoring nuclear localization of TDP-43.

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.

Described herein are aptamers capable of binding to human complement component 3 (C3) protein; compositions comprising a C3 binding aptamer with a C3-Protein; and methods of making and using the same.

An object of the present invention is to provide a polynucleotide having a modification site in a translated region with translation activity retained. The object can be achieved by a polynucleotide containing a translated region from a start codon to a stop codon, in which the translated region contains n codons, and the n is a positive integer of 2 or more, each of the n codons contains first, second and third nucleotides, and the first nucleotides in at least two codons of the n codons are sugar modified nucleotides.

There is provided an aptamer for dengue virus, optionally an aptamer for dengue virus NS1 protein. The aptamer comprising at least one unnatural base, wherein the unnatural base may be 7-(2thienyl)imidazo[4,5-b]pyridine (Ds), pyrrole2-carbaldehyde (Pa) or 2-nitro-4-propynylpyrrole (Px). The aptamers of the invention may be used to identify a dengue infection in a subject. Also provided are mixtures and kits comprising the aptamer.

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.

Provided herein are compositions related to Cas12b guide RNAs. Also provided herein are methods for modifying target polynucleotide sequences and methods of treating or preventing a condition in a subject in need thereof, such as conditions resultant from the expression of ANGPTL3 or mutations thereto.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.