Roche has struck a partnership with neuro-focused biotech Ascidian Therapeutics over an RNA editing platform. The deal sees the Boston-based Ascidian, a startup with preclinical programs in retinal, neurological and neuromuscular disorders, receive $42 million up front and up to $1.8 billion in milestones and commercial royalties. Under the agreement, Ascidian provides the Swiss pharma with access and rights to its potentially first-in-class RNA rewriting technology. The biotech’s RNA exon editing takes a different approach than that taken by gene and base therapies because it does not modify DNA and it does not require introduction of foreign enzymes. Instead, disease-causing mutations are corrected at the RNA level to restore native protein levels and patterns of expression. First the DNA with the genes’ introns and exons is transcribed into pre-mRNA. It then undergoes RNA splicing, where introns are removed and exons spliced together to form the mature mRNA, which is then translated into protein. In disease states, one or more genes may need to be replaced or edited. But most therapeutic constructs are too bulky to be administered in an adeno-associated virus (AAV) or other delivery vehicle.

To fashion a therapeutic, Ascidian uses computationally designed RNA exon editor molecules that replace mutated RNA exons simultaneously through pre-mRNA trans-splicing. An exon editor molecule excises disease-causing mutated RNA exons and replaces them, in a single reaction, with wild-type RNA exons. Ascidian’s editing molecule is small enough to fit viral or non-viral delivery vehicles, including lipid nanoparticles, which makes it particularly suited to correcting genes that are too big to be packaged into AAV delivery vectors. And because a single editing molecule can excise and replace multiple mutated exons, it can provide a one-time therapeutic with minimal risk of off-target DNA edits. The US FDA approved an IND for Ascidia’s first RNA exon-editing candidate, ACDN-01, now in phase 1/2 to treat Stargardt’s disease and other ABCA4 retinopathies.