Splice isoform-specific suppression of the CaV2.1 variant underlying spinocerebellar ataxia type 6

► Pathogenic CAG expansions alter Cav2.1 3′end splicing activity ► Altered-splicing activity leads to an increase in levels of polyQ-Cav2.1 variants ► Selective targeting of polyQ-encoding Cav2.1 splice isoforms using RNAi ► The RNAi machinery effectively processes human miR124-based artificial miRNAs.