| abstract |
The present disclosure provides antisense oligonucleotides, compositions, and methods that target a LIPA intron flanking exon 8, thereby modulating splicing of LIPA pre-mRNA to increase the level of LIPA mRNA molecules having exon 8, e.g., to provide a therapy for Wolman Disease or Cholesteryl Ester Storage Disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a LIPA pre-mRNA target sequence in a 5′-flanking intron, a 3′-flanking intron, or a combination of exon 8 and the 5′-flanking or 3′-flanking intron. |