A biotechnology company launched Wednesday by life sciences venture firm ATP is the latest startup to debut with a new twist on genetic editing.
With $50 million in funding, Boston-based Ascidian Therapeutics claims its RNA “exon editing” approach could match the durability of gene therapy while avoiding some of the risks that come with editing DNA.
Its platform is designed to correct for mutations in exons — the regions of DNA that contain information needed to make proteins. Ascidian aims to do this by replacing mutated exons with functional RNA copies as DNA is being converted into its chemical cousin.
The company will first target a genetic eye condition called Stargardt disease, which is the most common form of inherited macular degeneration and results in vision loss.
According to Ascidian, its technology can fix genetic errors that other editing approaches can’t, and can be applied to widely varied genes. Its lead program can replace more than 20 exons at a time, said Romesh Subramanian, Ascidian’s CEO.
“We are changing chapters in a book rather than whiting-out one letter at a time,” Subramanian, said in an interview with BioPharma Dive. Subramanian came to Ascidian from Dyne Therapeutics, a biotech he founded and led as CEO. He previously founded RNA specialist Translate Bio, which was bought by Sanofi last year.
Subramanian claims that Ascidian’s approach, by focusing on RNA, “maintains genome integrity” and thereby sidesteps concerns around off-target edits. His company also doesn’t rely on foreign enzymes to work, potentially easing immunogenicity risks, he added.
Along with Stargardt disease, Ascidian is looking at other eye conditions, neurological disorders and rare diseases. Subramanian declined to disclose how many drug research programs Ascidian plans to roll out.
Ascidian’s name is derived from a class of ocean-dwelling invertebrate creatures, which are sometimes known as sea squirts. These creatures use “RNA trans-splicing” to alter the RNA messengers used by their cells, a process that Ascidian plans to leverage to rewrite RNA for treating disease.
Ascidian is not ATP’s first foray into genetic medicine. Last year, Ascidian co-founder and ATP venture partner Michael Ehlers, a former Biogen executive, launched a startup called Intergalactic Therapeutics that focuses on non-viral gene therapy. ATP has also built a company called Replicate, which is developing another kind of RNA medicine.
“We think the RNA space is a big way of manipulating biology and treating disease across the board, and this approach we've taken to Ascidian defines a new class of RNA therapeutics,” Ehlers said.
The company expects to spend the rest of 2022 and 2023 on pre-clinical studies for its lead program, along with developing proof of concept for other candidates targeting neurological and neuromuscular diseases.
Gene editing research was catalyzed by the discovery of CRISPR, which has now been extended and adapted to support several different gene editing technologies. But biotech companies are also exploring RNA editing, which in part appeals to scientists because it doesn’t change the underlying DNA.
It has drawn in larger drugmakers, too: Roche and Eli Lilly have recently formed partnerships with Shape Therapeutics and ProQR Therapeutics, respectively, to develop treatments for a wide variety of diseases.