In one example of this combinatorial approach, ASOs inhibiting the activity of SMN-AS1, known to repress SMN1 transcription by recruiting PRC2 (polycomb repressive complex 2), delivered together with SMN2 splice-switching ASOs synergistically increased SMN protein expression and improved survival of a mouse model of severe SMA. This evidence concerns the gene SMN1 and proximal spinal muscular atrophy.