Ascidian Therapeutics Launches to Rewrite RNA

Ascidian Therapeutics has launched with a $50 million Series A financing from life sciences venture capital firm ATP. With a focus on treating human diseases by replacing mutated exons at the RNA level, 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 reducing risks associated with DNA editing and manipulation.

Ascidian is advancing its lead program for ABCA4 retinopathy including Stargardt disease while it progresses its pipeline of programs in ophthalmology, and neurological, neuromuscular, and rare diseases. Stargardt disease is the most common form of inherited macular degeneration and affects approximately 30,000 individuals in the United States alone. Stargardt disease is caused by mutations in the ABCA4 gene which can lead to progressive retinal degeneration and vision loss. Diseases caused by ABCA4 loss of function are examples of genetic disorders that cannot be addressed by standard gene replacement, given the large size of the gene, or by base editing, due to the high mutational variance of the affected gene.

Ascidian’s platform deploys high-throughput molecular biology in tandem with cutting-edge computational biology. A single Ascidian RNA editor can replace multiple mutated exons simultaneously, without modifying DNA, thereby limiting the risk of off-target DNA edits and expression of transgenes in off-target cell types. Moreover, the technology does not require the introduction of exogenous enzymes, reducing the risk of immunogenicity.

Ascidian’s technology is based on RNA trans-splicing, a phenomenon observed in multiple organisms, including ascidians—ancient ancestors of vertebrates—which deploy trans-splicing to re-engineer their transcriptome. As applied by Ascidian, RNA trans-splicing enables excision of disease-causing exons and their replacement with wild-type exons in a single reaction to treat disease. (Source: Ascidian Therapeutics Website, 12 October, 2022)