ASSOCIATION INSTITUT DE MYOLOGIE;SORBONNE UNIVERSITE;UNIVERSITAT BERN;CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE;INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
发明人:
Daniel Schumperli,Christian Leumann,Denis Furling,Luis Garcia,Thomas Voit
申请号：
US15428385
公开号：
US10465191B2
申请日:
2017.02.09
申请国别(地区):
US
年份:
2019
代理人:
摘要：
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.
