UNASSIGNED: @entity2057 ( @entity2057 ) is a fatal @entity74 caused by survival motor neuron ( @entity11280 ) @entity1887 due to @entity11280 mutations. Boosting @entity23247 expression is a potential therapy for @entity2057 . @entity23247 has identical coding sequence as @entity11280 except for a silent C-to-T transition at the 6th @entity4334 of exon 7, converting a splicing enhancer to a silencer motif. Consequently, most @entity23247 transcripts lack exon 7. More than ten putative splicing regulatory elements (SREs) were reported to regulate exon 7 splicing. To investigate the relative strength of each negative SRE in inhibiting exon 7 inclusion, antisense oligonucleotides (AONs) were used to mask each element, and the fold increase of full-length @entity11280 transcripts containing exon 7 were compared. The most potent negative SREs are at intron 7 (in descending order): ISS-N1, 3' splice site of exon 8 (ex8 3'ss) and ISS+100. Dual-targeting AONs were subsequently used to mask two nonadjacent SREs simultaneously. Notably, masking of both ISS-N1 and ex8 3'ss induced the highest fold increase of full-length @entity11280 transcripts and proteins. Therefore, efforts should be directed towards the two elements simultaneously for the development of optimal AONs for @entity2057 therapy.

Dual Masking of Specific Negative Splicing Regulatory Elements Resulted in Maximal Exon 7 Inclusion of XXXX Gene.

@entity23247 :: ('6607', 'Gene') :: ['SMN2'] @entity1887 :: ('MESH:D000309', 'Disease') :: ['protein insufficiency'] @entity4334 :: ('D009711', 'Chemical') :: ['nucleotide'] @entity74 :: ('MESH:D030342', 'Disease') :: ['autosomal recessive disease'] @entity11280 :: ('6606', 'Gene') :: ['SMN1', 'SMN'] @entity2057 :: ('MESH:D009133', 'Disease') :: ['Spinal muscular atrophy', 'SMA']
@entity23247 :: (6607,Gene) :: ['SMN2']
