Jay Barth, MD, on Ascidian Therapeutics' Developments in Gene Therapy

“We are developing a new way of administering gene therapy, and, through a mechanism known as exon editing of RNA, we're able to restore protein to genes that are deficient or non-functional, due to mutations, in which cases the gene therapy and gene editing technologies that are currently available are not applicable. In particular, genes that are of large size and beyond the carrying capacity of current AAV.”

At the 2023 Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, in New Orleans, Louisiana, CGTLive^™’s sister publication, Ophthalmology Times^® talked with Jay Barth, MD, about the work at Ascidian Therapeutics and their research into developing a new way to administer gene therapy. The company presented new 6-month durability data from the program targeting ABCA4 retinopathies, data that demonstrate an efficient and durable RNA exon editing approach with transsplicing in a large animal.^1,2

Presented by Shimyn Slomovic, PhD, the director and head of molecular biology at Ascidian, the data displayed that exon editors “can efficiently replace the 5’ half of the 7 kb ABCA4 coding sequence, which covers ~60% of known patient mutations, resulting in protein rescue in vitro in an engineered mutant cell line, as well as in Non-Human Primate (NHP) retina following subretinal injection of an AAV-encoded Exon Editor construct,” they wrote.¹ Slomovic and coauthors noted that the report suggests that there is translational viability with this therapeutic strategy.

Previously, Barth presented an update on Ascidian’s lead program and its findings in RNA exon editing for patients with Stargardt disease and other ABCA4-related retinopathies at the Retinal Cell and Gene Therapy Innovation Summit 2023. While at ARVO, he offered insight into the specifics of the approach that Ascidian is developing and the science behind it, what has been shown to this point, and the potential of a submission to the FDA.

Click here for more coverage of ARVO 2023.

REFERENCES
1. Slomovic S, Doi A, Gray JM, et al. ABCA4 RNA exon editing in vitro and in vivo. Presented at: ARVO 2023; April 23-27; New Orleans, LA. Poster B0149.
2. Ascidian Therapeutics to Present Data From Its Lead Program Targeting ABCA4 Retinopathies at the Retinal Cell and Gene Therapy Innovation Summit and ARVO 2023 Annual Meeting. News release. Ascidian Therapeutics. April 18, 2023. Accessed May 1, 2023. https://ascidian-tx.com/wp-content/uploads/2023/04/Ascidian-ARVO-FFB-Release-FINAL_18-April-2023.pdf