Compositions and methods for treatment of spinocerebellar ataxias

Abstract

The present disclosure provides single- or double-stranded interfering RNA molecules (e.g., siRNA) that target an ataxin-3 (ATXN3) gene. The interfering RNA molecules may contain specific patterns of nucleoside modifications and internucleoside linkage modifications, as pharmaceutical compositions including the same. The siRNA molecules may be branched siRNA molecules, such as di-branched, tri-branched, or tetra-branched siRNA molecules. The disclosed siRNA molecules may further feature a 5′ phosphorus stabilizing moiety and/or a hydrophobic moiety. Additionally, the disclosure provides methods for delivering the siRNA molecule of the disclosure to the central nervous system of a subject, such as a subject identified as having a spinocerebellar ataxia (e.g., spinocerebellar ataxia type 3).

Dependencies are inferred from the claim text.