Rewriting RNA – Ascidian’s exon editing platform
Expanding the therapeutic possibilities of RNA medicine for patients
The transcription of DNA into RNA is a fundamental biological process.
During transcription, cellular machinery transcribes a gene’s introns and exons into a pre-mRNA molecule. Then, during the process of RNA splicing, introns are removed and exons are spliced together to form mature mRNA that is translated into protein. Mutations anywhere in these exons may result in malformed proteins, often causing severe disease.
What if we could identify and correct these mutations to slow, stop, or even reverse disease?
The large size and high mutational variance of many genes places them beyond the reach of existing gene editing and base editing approaches.
Ascidian Therapeutics is taking a fundamentally different approach by editing exons at the RNA level
RNA exon editing produces mRNA levels consistent with intact gene expression circuitry
By replacing mutated exons, Ascidian’s technology enables therapeutic targeting of large genes and genes with high mutational variance while maintaining native gene expression patterns and levels. This approach is designed to provide the durability of gene therapy while sharply reducing risks associated with DNA editing and manipulation.
Exon editing explained
Ascidian's first-of-its-kind RNA exon editing platform deploys high-throughput molecular biology in tandem with cutting-edge computational biology to design novel RNA exon editor molecules.
A single exon editing molecule can be used to replace multiple mutated exons simultaneously through pre-mRNA trans-splicing, without modifying DNA and without requiring the introduction of foreign enzymes. Ascidian’s exon editing takes place at the RNA level, thereby limiting risk of off-target DNA edits or expression of transgenes in inappropriate cell types.
RNA exon editing excises mutated exons and replaces them with wild-type exons in a single reaction to restore normal protein production
Since only disease-causing exons in a gene need to be replaced, the exon editing molecule is small enough to fit in AAV or other viral or non-viral delivery vehicles, including lipid nanoparticles. Ascidian’s platform is versatile, allowing the RNA exon editing therapeutics to be administered using a delivery vehicle targeted specifically to the location where post-transcriptional editing is needed to treat disease.