TS-005640 — This new gene editing system is based on prime editing, connecting N-terminal mutations in the DMD gene to enable expression of full-length or near-full-length dystrophin. This system also has the advantage of stably incorporating edits into the genome. Current treatments such as exon skipping and microdystrophin gene replacement have not successfully halted disease progression in clinical trials, leaving a critical need for therapies that restore full-length or near-full-length dystrophin, especially for patients with mutations in the N-terminal region of the gene, which have been under-addressed.

TS-005494 — A new approach to correcting mutations in the DMD gene upstream of exon 20 was achieved by inserting into the native intron 19, which holds the sequence of exons 1-19, along with a new promoter. This method builds on previous insertion approaches, bypassing any upstream truncating mutations and allowing full-length dystrophin expression when spliced. The insertion is made through twin prime editing to avoid any double-stranded break of the genome, and can be translated into a therapy for patients.