Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Sorbonne Université

Universitât Bern

Association Institut De Myologie

Daniel Schumperli

Thomas Voit

Luis Garcia

Christian Leumann

Denis Furling

Provided are tricyclo-DNA (tc-DNA) AON and methods employing tc-DNA AON for modifying splicing events that occur during pre-mRNA processing. Tricyclo-DNA (tc-DNA) AON are described that may be used to facilitate exon skipping or to mask intronic silencer sequences and/or terminal stein-loop sequences during pre-mRNA processing and to target RNase-mediated destruction of processed mRNA. Tc-DNA AON described herein may be used in methods for the treatment of Duchenne Muscular Dystrophy by skipping a mutated exon 23 or exon 51 within a dystrophin gene to restore functionality of a dystrophin protein; in methods for the treatment of Spinal Muscular Atrophy by masking an intronic silencing sequence and/or a terminal stem-loop sequence within an SMN2 gene to yield modified functional SMN2 protein, including an amino acid sequence encoded by exon 7, which is capable of at least partially complementing a non-functional SMN1 protein; and in methods for the treatment of Steinert's Myotonic Dystrophy by targeting the destruction of a mutated DM1 mRNA comprising 3'-terminal CUG repeats.

Tricyclo-DNA antisense oligonucleotides, compositions, and methods for the treatment of disease

Growing community of inventors

Bern, Switzerland

Daniel Schumperli