Methods for the treatment of weight-related disorders, including obesity and disorders associated with obesity, as well as underweight and disorders associated with underweight, by modulating Rlim levels.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

A compound for forming a conjugate with an active agent such as an oligonucleotide having a structure represented by Formula (321). The present disclosure also provides a corresponding conjugate. The conjugate of the present disclosure can specifically target hepatocytes, thereby effectively solve the problems associated with delivery of oligonucleotide drugs in vivo, and have low toxicity and excellent delivery efficiency while maintaining high stability for the delivered oligonucleotide. ##STR00001##

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.

Therapeutic oligonucleotides comprising universal pharmacokinetic (PK)-modifying anchors are provided. Methods for treating diseases or disorders comprising administering to a subject a therapeutic oligonucleotide comprising one or more universal PK-modifying anchors are provided.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

The present disclosure relates to polypeptides, such as fibronectin type III (FN3) domains that can bind CD71, their conjugates, isolated nucleotides encoding the molecules, vectors, host-cells, as well as methods of making and using the same.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.

Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5′ end to 3′ end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the angiotensin converting enzyme 2 (ACE2) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an ACE2 gene and to methods of treating or preventing an ACE2-associated disease, e.g., COVID-19, in a subject.