Compositions and methods for treating neurological disorders

Abstract

The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNAs) targeting chromosome 9 open reading frame 72 (C9orf72). The interfering RNA molecules, as well as pharmaceutical compositions containing them, may contain specific patterns of nucleoside and internucleoside linkage modifications. The siRNA molecules may be branched siRNA molecules (e.g., bi-, tri-, or tetra-antennary siRNA molecules). The disclosed siRNA molecules may further be characterized by a 5' phosphorus-stabilizing moiety and / or a hydrophobic moiety. Furthermore, the present disclosure provides methods for delivering the siRNA molecules of the present disclosure to the central nervous system of a subject (e.g., a subject identified as suffering from amyotrophic lateral sclerosis or frontotemporal dementia).

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