The University of Texas System

Ionis Pharmaceuticals, Inc.

Jiaxin Hu

David R Corey

Masayuki Matsui

Eric E Swayze

Thazha P Prakash

Jing Liu

Dongbo Yu

Dinah W Y Sah

Venkateswara V Mootha

Provided herein are compositions and methods for reducing expression of C9orf72 transcripts in cells containing expanded intronic GGGGCC regions, including those in subjects having or at risk of developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

Allele selective inhibition of mutant C9orf72 foci expression by duplex RNAs targeting the expanded hexanucleotide repeat

Described are compounds and methods useful in the treatment of Fuchs' Endothelial Corneal Dystrophy (FECD).

Treatment of Fuchs' endothelial corneal dystrophy

Provided herein are compositions and methods for reducing expression of C9orf72 transcripts in cells containing expanded intronic GGGGCC regions, including those in subjects having or at risk of developing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Provided herein are a double-stranded oligonucleotides of 13 to 22 nucleobases in length targeting a GGGGCC expanded repeat region in an intron of C9orf72, comprises (a) 3-5 central mismatches (within bases 9-14) within a target sequence comprising the expanded repeat sequence, or (h) 3-5 mismatches outside of the seed sequence (bases 2-8 within the guide strand complementary to the expanded repeat sequence).

Allele selective inhibition of mutant C9orf72 foci expression by duplex RNAS targeting the expanded hexanucleotide repeat

Described are compounds and methods useful for the treatment and investigation of diseases and disorders associated with expanded repeat-containing RNA molecules. In certain embodiments, compounds and methods useful for the modulation of ATXN-3 pre-mRNA are described. In certain embodiments, compounds and methods useful for the modulation of ATN-1 mRNA are described.

Methods and compounds useful in conditions related to repeat expansion

The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntingtin Disease Protein and Ataxin-3 using double-stranded RNAs and nucleic acid analogs. Chemically-modified RNAs having at least one mismatch as compared to the target CAG repeat sequence are specifically contemplated.

Selective inhibition of polyglutamine protein expression

The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntington using nucleic acid analogs. Peptide nucleic acids and locked nucleic acids are particularly useful analogs.

The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntingtin using nucleic acid analogs. Peptide nucleic acids and locked nucleic acids are particularly useful analogs.

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Coppell, TX, United States of America

Jiaxin Hu