Abstract: The present disclosure provides antisense oligonucleotides, compositions, and methods that target a ABCA4 exon or intron flanking an exon, thereby modulating splicing of ABCA4 pre-mRNA to increase the level of wild type ABCA4 mRNA molecules, e.g., to provide a therapy for retinitis pigmentosa, cone-rod dystrophy, or Stargardt disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a ABCA4 pre-mRNA target sequence in an intron, 5?-flanking intron, a 3?-flanking intron, or a combination of an exon and the 5?-flanking or 3?-flanking intron.

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.

Abstract: The invention features isolated mRNAs encoding at least one intracellular binding domain, including mRNAs comprising one or more modified nucleobase and preferably lacking an encoded scaffold polypeptide, and methods of using the same, for example, for inducing apoptosis and/or treating cancer (e.g., liver cancer or colorectal cancer).

Abstract: The invention features isolated mRNAs encoding fusion polypeptides comprising a Stefm A (SteA) scaffold polypeptide and one or more binding polypeptides, such as one or more Bc1-2 homology 3 (BH3) domains, including mRNAs comprising one or more modified nucleobase, and methods of using the same, for example, for inducing apoptosis and/or treating cancer (e.g., liver cancer or colorectal cancer).