The present disclosure provides methods and compositions for the treatment of NF-1 and NF-1 mediated conditions. The present disclosure further provides for methods of exon skipping and exon retention and compositions for use in such methods. Such methods of exon skipping and exon retention may be used in the methods of treatment discussed herein. The present disclosure further provides new therapeutic compounds, particularly oligonucleotides, including antisense oligonucleotides, for use in the methods described herein.

The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group.

Described are short interfering nucleic acid (siNA) molecules comprising modified nucleotides, compositions, and methods and uses thereof.

The invention relates to neurodegenerative disorders, and in particular to novel oligonucleotides for treating such conditions, for example Alzheimer's disease. The invention provides novel antisense oligonucleotides, and compositions comprising such oligos, and therapies and methods for treating neurodegenerative disorders. The invention includes genome editing techniques for achieving similar results as using the novel antisense oligonucleotides.

The present specification provides a drug that causes highly-efficient skipping of exon 50 in the human dystrophin gene. The present specification provides an antisense oligomer which induces skipping of exon 50 in the human dystrophin gene.

The present specification provides a drug that causes highly-efficient skipping of exon 50 in the human dystrophin gene. The present specification provides an antisense oligomer which induces skipping of exon 50 in the human dystrophin gene.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Disclosed herein include guide RNA (gRNA), such as single gRNA (sgRNA), and compositions thereof, comprising 2′-O-methyldithiomethyl modified sugar moieties which can be reduced to 2′-O-methanethiol groups in the reducing environment of cells and then converted (e.g., spontaneously converted) to 2′-OH. The resultant gRNA can bind to and direct the activity of an RNA-guided endonuclease (e.g., Cas9).

The present invention relates to antisense oligonucleotides that are complimentary to SOD1, leading to decreased expression of SOD1. Reduced expression of SOD1 is beneficial in medical disorders such as Amyotrophic Lateral Sclerosis.

The present disclosure relates to multimeric oligonucleotides comprising subunits, each of the subunits independently comprises a single-stranded or double-stranded oligonucleotide. Each of the subunits is joined to another subunit by a covalent linker, and at least one subunit comprises at least one partial single-stranded oligonucleotide. The present disclosure also relates to methods of synthesizing the multimeric oligonucleotides and the methods of using the multimeric oligonucleotides disclosed herein.