Splice-switching antisense oligonucleotide (SSOs) technology utilize modified RNA to disrupt pre-mRNA splicing. When mRNA is first transcribed from DNA, it contains regions known as introns, which do not contribute to the final protein product. These introns are removed, and the regions that do contribute to the finalized protein product, exons, are ligated together. Aberrations in pre-mRNA splicing contribute to a myriad of human diseases, such as Duchenne Muscular Dystrophy. Cryptic splice sites are when a pre-mRNA has incorrect splicing sequences in a pre-mRNA. This can be a result of a single point mutation, causing a deletion in the entire pre-mRNA, leading to a truncated protein.

SSOs are engineered to bind to these faulty pre-mRNAs, and disrupt the intron splicing machinery from binding and creating an aberrant transcript. They can modulate splicing patterns to create an mRNA that produces a “lesser of two evils (less worse)” protein.

Of course, CRISPR is likely more suited to alter single nucleotide substitution mutations, but that’s an application of RNA-based technologies that isn’t talked about as much. Splicing can be a big problem, especially with cryptic splice sites.