Universitât Bern

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

Association Institut De Myologie

Other

Sorbonne Université

Université Pierre Et Marie Curie (paris 6)

Universitat Ber

Université Pierre Et Marie Curie

Christian Leumann

Thomas Voit

Luis Garcia

Damien Evéquoz

Branislav Dugovic

Denis Furling

Daniel Schumperli

Jory Liétard

Daniel Schümperli

Oligomers can be prepared from bicyclic nucleoside. The nucleosides can be a compound of formula (I)

Bicyclic nucleosides and oligomers prepared therefrom

Oligomers can be prepared from bicyclic nucleosides. The nucleosides can be a compound of formula (I) 

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

The present invention provides fluorine substituted tricyclic nucleosides of formula (I) wherein: the substituents are as defined in the claims. The present invention further provides oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound enhances one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions. 

Tricyclic nucleosides and oligomeric compounds prepared therefrom

The present invention relates to a nucleic acid molecule containing a sequence of tricyclo nucleosides joined by internucleoside phosphorothioate linkage. The invention also relates to synthetic antisense oligonucleotides and to methods employing the same.

Tricyclo-phosphorothioate DNA

The present invention provides novel tricyclic nucleosides and oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound is expected to enhance one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

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Bern, Switzerland

Christian Leumann