| abstract |
The present invention relates, inter alia, to oligonucleotides, compositions and related methods. Among others, the present invention relates to the recognition that structural elements of oligonucleotides, such as a base sequence, chemical modifications (e.g., modifications of sugars, bases and / or internucleotide linkages) or associated motifs, conjugation with additional chemical moieties, and / or stereochemistry [eg, stereochemistry of chiral centers of the carbon skeleton (chiral internucleotide linkages)], and / or associated motifs, can have a significant impact on properties and oligonucleotide activities, for example, inactivation capacity, stability, distribution, etc. In some embodiments, the oligonucleotides decrease the expression, activity, and / or level of a C9orf72 gene, including, but not limited to, a gene comprising a repetition expansion, or an associated gene product. In some embodiments, the present invention provides methods of treating diseases using oligonucleotide compositions according to the present invention, for example, in the treatment of C9orf72-related disorders. |