The elucidation of the mechanisms underlying maturation/splicing of pre-messenger RNA has opened the prospect of new RNA-targeting allele specific therapies. Effectively, by Watson and Crick pair association, the use of antisense oligonucleotides (ASO) masking splicing determinant sequences allows highly selective rehabilitation of mutated mRNAs.
For example, it is now possible to selectively destroy or correct the reading frame of a target mRNA by the skipping/exclusion of a deleterious exon (e.g., the dystrophin-coding DMD gene in the case of Duchenne Muscular Dystrophy) or the re-inclusion of an exon discarded by the remote effect of a mutation (e.g., the SMN2 gene in the case of spinal amyotrophy - SMA). Specifically, the exonic organization of the dystrophin gene (79 exons) and the fact that the dystrophin protein contains many non-essential areas at its center make DMD a textbook case for the development of therapeutic ASO.
One of the company's flagship activities is the development of a new generation of tricyclo-DNA class (tcDNA), antisense oligonucleotides (ASO), which are third generation non-natural nucleotidic analogs hybridizing with their target RNA with higher affinity in comparison to the existing offer. ASO-tcDNA is compatible with intravenous administration and efficiently reaches the entire skeletal musculature and the heart, the primary targets in Duchenne Muscular Dystrophy.
The company has perpetuated this technology by increasing its capacity for large-scale synthesis of tcDNA phosphoramidites required for the production of ASO-tcDNA; it has also designed several ASO candidates, among which the first one targeting exon 51 of the DMD gene in the case of Duchenne Muscular Dystrophy, which is in development for a Phase 1/2a clinical trial in the future. Finally, this knowledge is transposable to other diseases for which new ASO-tcDNA are being developed.