Patent · US Active

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

US10465191B2 · kind B2 · utility

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Key dates

Filing dateFeb 9, 2017
Grant dateNov 5, 2019
Priority date
Expiry dateFeb 9, 2037

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC12N2320/33
  • WIPO fieldPharmaceuticals
  • WIPO sectorChemistry

Abstract

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.

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