This disclosure relates to novel SARS-CoV-2 targeting sequences. Novel SARS-CoV-2 targeting oligonucleotides for the treatment of SARS-CoV-2 infection are also provided.

The present disclosure provides methods of treating a subject having a metabolic disorder or is at risk of developing a metabolic disorder or preventing a subject from developing a metabolic disorder, and methods of identifying subjects having an increased risk of developing a metabolic disorder.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle dystrophy (DM1).

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX.sup.1X.sup.2rCrUrGrCrUrGrCrUrG (I), wherein X.sup.1 and X.sup.2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X.sup.1 and X.sup.2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

Disclosed herein include compositions and methods of modulating protein expression that utilizes an activator or a repressor of a non-sense mediated RNA decay switch exon (NSE). In some embodiments, also included herein are compositions and methods of modulating protein expression that uses an agent that targets a transposed element.

The present invention concerns the treatment of prostate cancer and particularly castration resistant prostate cancer (CRPC). The Heat Shock Protein Hsp27, a chaperone protein, has been long demonstrated as a driver of Castration Resistance Prostate Cancer (CRPC). In the light of identification of the molecular mechanisms, the inventor determined that the Probable ATP-dependent RNA helicase DDX5 is an interactor of Hsp27 and DDX5's expression is modulated by Hsp27. They confirmed that DDX5 overexpression is correlated to the aggressiveness of the tumor, to the CRPC emergency and to the biochemical recurrence risk. They also developed DDX5-targeting antisense oligonucleotides for research purpose and clinical application. Thus, the invention relates to an inhibitor of DDX5 wherein said inhibitor reduces the expression and/or activity of DDX5 in a subject in need thereof and targets the gene or the mRNA of DDX5.

The present invention concerns an ubiquitin ligase inhibitor for use for preventing and/or treating a disease linked with cerebral hypoperfusion, and an in vitro screening method for the identification of a candidate compound suitable for preventing and/or treating a disease linked with cerebral hypoperfusion.

The present disclosure relates to modified extracellular vesicles, e.g., exosomes, comprising an antisense oligonucleotide (ASO), which is capable of reducing and/or inhibiting expression of KRAS mRNA and/or KRAS protein. ASOs that can be used with the modified extracellular vesicles are also disclosed. Also provided herein are methods for using the exosomes and ASOs to treat and/or prevent diseases, such as cancer.

Provided herein are method of treating cancer using agents that inhibit the interaction between Methyltransferase like 3 (METTL3) and Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3h), and optionally agents that inhibit Bromodomain-containing protein 4 (BRD4). The present disclosure demonstrates the topology of individual polyribosomes with single METTL3 foci found in close proximity to 5′ cap-binding proteins, revealing a previously unknown direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h).