SMN2 and spinal muscular atrophy, type 1: Here we show that three ExSpe U1s previously reported to be active in SMN2 minigene assays are able to fully reverse E7 aberrant splicing in fibroblasts from individuals with the severe SMA type I. Transduction of primary cells from SMA-affected individuals with lentiviral particles expressing SMN-specific ExSpe U1s restores normal E7 transcript levels, leading to the production of physiological amounts of functional SMN protein.