Regulation of gene expression by alternative splicing aptamer-mediated regulation

摘要

The present invention provides platforms and methods of using the platforms to modulate the expression of target genes using exposure to aptamer ligands (eg, small molecules). The platform features a polynucleotide gene regulatory cassette that is located within the target gene and includes a synthetic riboswitch located in the context of a 5 'intron-selective exon-3' intron. Riboswitches have effector and sensor regions (eg, aptamers that bind to small molecule ligands) so that in the absence of ligand, alternative exons are spliced into the target gene mRNA, thereby preventing target gene expression. Including. When a ligand is present, alternative exons are not spliced to the target gene mRNA, thereby providing target gene expression.