The present invention provides compounds comprising oligonucleotides complementary to a fibronectin transcript. Certain such compounds are useful for hybridizing to a fibronectin transcript, including but not limited to a fibronectin transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the fibronectin transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with fibrosis. In certain embodiments, such compounds are used to treat one or more symptoms associated with renal fibrosis.

Provided herein are antisense oligonucleotides and prophylactic and therapeutic methods featuring such oligonucleotides. These oligonucleotides and methods are useful for treating or preventing ataxia telangiectasia in a subject. Specifically, the disclosure provides antisense nucleobase oligomers each comprising (8-40) nucleobases, wherein at least 90% of said nucleobases or more than (8) consecutive nucleobases of the oligomer are complementary to a nucleic acid sequence in an Ataxia-Telangiectasia Mutated (ATM) allele comprising a mutation associated with aberrant splicing.

The present disclosure relates generally to compositions and methods suitable for treating a disorder associated with loss-of-function mutations in SYNGAP1. More specifically, the disclosure relates to methods for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1, and to antisense oligonucleotides specific for SYNGAP1 and their use for treating a disorder associated with heterozygous loss-of-function mutations of SYNGAP1.

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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The invention is directed to one or more antisense polynucleotides and their use in pharmaceutical compositions in a strategy to induce exon skipping in the γ-sarcoglycan gene in patients suffering from Limb-Girdle Muscular Dystrophy-2C (LGMD2C) or in patients at risk of such a disease. The invention also provides methods of preventing or treating muscular dystrophy, e.g., LGMD2C, by exon skipping in the gamma sarcoglycan gene using antisense polynucleotides. Accordingly, in some aspects the invention provides an isolated antisense oligonucleotide, wherein the oligonucleotide specifically hybridizes to an exon target region of a γ-sarcoglycan RNA. In another aspect, the the invention provides a method of inducing exon-skipping of a gamma sarcoglycan RNA, comprising delivering an antisense oligonucleotide or a composition to a cell.

Provided are peptide nucleic acid derivatives targeting a 3′ splice site of the human SNAP25 pre-mRNA. The peptide nucleic acid derivatives potently induce at least a splice variant of the human SNAP25 mRNA in cells, and are useful to safely treat dermatological indications or conditions involving the expression of the human SNAP25 protein by topical administration.

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.

The present application relates to the field of cancer, particularly that of cancers with high MDM4 protein levels (such as melanoma, breast, colon or lung cancers, glioblastoma, retinoblastoma, etc.). It is shown herein that direct and selective inhibition of MDM4, e.g., by antisense RNA, leads to growth inhibition of cancer cells and sensitization to chemo or targeted therapies. Also provided are simple ways of determining which patients are most amenable for such treatment by comparing specific transcript levels.

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

The present disclosure relates generally to compounds comprising oligonucleotides complementary to a cystic fibrosis transmembrane conductance regulator (CFTR) RNA transcript. Certain such compounds are useful for hybridizing to a CFTR RNA transcript, including but not limited to a CFTR RNA transcript in a cell. In certain embodiments, such hybridization results in modulation of splicing of the CFTR transcript. In certain embodiments, such compounds are used to treat one or more symptoms associated with Cystic Fibrosis.