Branched oligonucleotides

A branched oligonucleotide compound, capable of mediating RNA silencing in a neuronal cell, comprising two or more nucleic acid sequences, wherein the nucleic acid sequences (N) are connected to one another by one or more moieties selected from a linker (L), a spacer (S) and optionally a branching point (B),

• wherein each nucleic acid sequence is double-stranded and comprises a sense strand and an antisense strand, wherein the sense strand and the antisense strand each have a 5′ end and a 3′ end, and wherein the sense strand and the antisense strand each comprises >80% chemically-modified nucleotides,
• wherein the nucleotides at positions 1 and 2 from the 5′ end of the sense and antisense strands are connected to adjacent nucleotides via phosphorothioate linkages,
• wherein each antisense strand comprises at least 15 contiguous nucleotides, wherein each sense strand comprises at least 15 contiguous nucleotides and has complementarity to the antisense strand, and wherein the antisense strand has complementarity to a target mRNA in the neuronal cell, and
• wherein the antisense strand is complementary to a target mRNA in a neuronal cell.